Influenza-Specific Antibody-Dependent Phagocytosis
Identifieur interne : 000C73 ( Ncbi/Merge ); précédent : 000C72; suivant : 000C74Influenza-Specific Antibody-Dependent Phagocytosis
Auteurs : Fernanda Ana-Sosa-Batiz [Australie] ; Hillary Vanderven [Australie] ; Sinthujan Jegaskanda [Australie] ; Angus Johnston [Australie] ; Steven Rockman [Australie] ; Karen Laurie [Australie] ; Ian Barr [Australie] ; Patrick Reading [Australie] ; Marit Lichtfuss [Australie] ; Stephen J. Kent [Australie]Source :
- PLoS ONE [ 1932-6203 ] ; 2016.
Abstract
Immunity to human influenza A virus (IAV) infection is only partially understood. Broadly non-neutralizing antibodies may assist in reducing disease but have not been well characterized.
We measured internalization of opsonized, influenza protein-coated fluorescent beads and live IAV into a monocytic cell line to study antibody-dependent phagocytosis (ADP) against multiple influenza hemagglutinin (HA) subtypes. We analyzed influenza HA-specific ADP in healthy human donors, in preparations of intravenous immunoglobulin (IVIG), and following IAV infection of humans and macaques.
We found that both sera from healthy adults and IVIG preparations had broad ADP to multiple seasonal HA proteins and weak cross-reactive ADP to non-circulating HA proteins. The ADP in experimentally influenza-infected macaque plasma and naturally influenza-infected human sera mediated phagocytosis of both homologous and heterologous IAVs. Further, the IAV phagocytosed in an antibody-mediated manner had reduced infectivity
We conclude that IAV infections in humans and macaques leads to the development of influenza-specific ADP that can clear IAV infection
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DOI: 10.1371/journal.pone.0154461
PubMed: 27124730
PubMed Central: 4849649
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Influenza-Specific Antibody-Dependent Phagocytosis</title><author><name sortKey="Ana Sosa Batiz, Fernanda" sort="Ana Sosa Batiz, Fernanda" uniqKey="Ana Sosa Batiz F" first="Fernanda" last="Ana-Sosa-Batiz">Fernanda Ana-Sosa-Batiz</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Vanderven, Hillary" sort="Vanderven, Hillary" uniqKey="Vanderven H" first="Hillary" last="Vanderven">Hillary Vanderven</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Jegaskanda, Sinthujan" sort="Jegaskanda, Sinthujan" uniqKey="Jegaskanda S" first="Sinthujan" last="Jegaskanda">Sinthujan Jegaskanda</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Johnston, Angus" sort="Johnston, Angus" uniqKey="Johnston A" first="Angus" last="Johnston">Angus Johnston</name><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Drug Delivery, Disposition and Dynamics laboratory, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Drug Delivery, Disposition 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Melbourne, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>bioCSL Ltd, Parkville, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>bioCSL Ltd, Parkville, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Laurie, Karen" sort="Laurie, Karen" uniqKey="Laurie K" first="Karen" last="Laurie">Karen Laurie</name><affiliation wicri:level="3"><nlm:aff id="aff005"><addr-line>WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Barr, Ian" sort="Barr, Ian" uniqKey="Barr I" first="Ian" last="Barr">Ian Barr</name><affiliation wicri:level="3"><nlm:aff id="aff005"><addr-line>WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Reading, Patrick" sort="Reading, Patrick" uniqKey="Reading P" first="Patrick" last="Reading">Patrick Reading</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff005"><addr-line>WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Lichtfuss, Marit" sort="Lichtfuss, Marit" uniqKey="Lichtfuss M" first="Marit" last="Lichtfuss">Marit Lichtfuss</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Kent, Stephen J" sort="Kent, Stephen J" uniqKey="Kent S" first="Stephen J." last="Kent">Stephen J. Kent</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff006"><addr-line>Melbourne Sexual Health Centre, Central Clinical School, Monash University, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Melbourne Sexual Health Centre, Central Clinical School, Monash University, 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Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Vanderven, Hillary" sort="Vanderven, Hillary" uniqKey="Vanderven H" first="Hillary" last="Vanderven">Hillary Vanderven</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Jegaskanda, Sinthujan" sort="Jegaskanda, Sinthujan" uniqKey="Jegaskanda S" first="Sinthujan" last="Jegaskanda">Sinthujan Jegaskanda</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Johnston, Angus" sort="Johnston, Angus" uniqKey="Johnston A" first="Angus" last="Johnston">Angus Johnston</name><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Drug Delivery, Disposition and Dynamics laboratory, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Drug Delivery, Disposition and Dynamics laboratory, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash University, Parkville, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash University, Parkville</wicri:regionArea><wicri:noRegion>Parkville</wicri:noRegion></affiliation></author><author><name sortKey="Rockman, Steven" sort="Rockman, Steven" uniqKey="Rockman S" first="Steven" last="Rockman">Steven Rockman</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>bioCSL Ltd, Parkville, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>bioCSL Ltd, Parkville, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Laurie, Karen" sort="Laurie, Karen" uniqKey="Laurie K" first="Karen" last="Laurie">Karen Laurie</name><affiliation wicri:level="3"><nlm:aff id="aff005"><addr-line>WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Barr, Ian" sort="Barr, Ian" uniqKey="Barr I" first="Ian" last="Barr">Ian Barr</name><affiliation wicri:level="3"><nlm:aff id="aff005"><addr-line>WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Reading, Patrick" sort="Reading, Patrick" uniqKey="Reading P" first="Patrick" last="Reading">Patrick Reading</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff005"><addr-line>WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Lichtfuss, Marit" sort="Lichtfuss, Marit" uniqKey="Lichtfuss M" first="Marit" last="Lichtfuss">Marit Lichtfuss</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Kent, Stephen J" sort="Kent, Stephen J" uniqKey="Kent S" first="Stephen J." last="Kent">Stephen J. Kent</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff006"><addr-line>Melbourne Sexual Health Centre, Central Clinical School, Monash University, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Melbourne Sexual Health Centre, Central Clinical School, Monash University, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff007"><addr-line>ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Parkville, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Parkville</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="sec001"><title>Background</title><p>Immunity to human influenza A virus (IAV) infection is only partially understood. Broadly non-neutralizing antibodies may assist in reducing disease but have not been well characterized.</p></sec><sec id="sec002"><title>Methods</title><p>We measured internalization of opsonized, influenza protein-coated fluorescent beads and live IAV into a monocytic cell line to study antibody-dependent phagocytosis (ADP) against multiple influenza hemagglutinin (HA) subtypes. We analyzed influenza HA-specific ADP in healthy human donors, in preparations of intravenous immunoglobulin (IVIG), and following IAV infection of humans and macaques.</p></sec><sec id="sec003"><title>Results</title><p>We found that both sera from healthy adults and IVIG preparations had broad ADP to multiple seasonal HA proteins and weak cross-reactive ADP to non-circulating HA proteins. The ADP in experimentally influenza-infected macaque plasma and naturally influenza-infected human sera mediated phagocytosis of both homologous and heterologous IAVs. Further, the IAV phagocytosed in an antibody-mediated manner had reduced infectivity <italic>in vitro</italic>.</p></sec><sec id="sec004"><title>Conclusion</title><p>We conclude that IAV infections in humans and macaques leads to the development of influenza-specific ADP that can clear IAV infection <italic>in vitro</italic>. Repeated exposure of humans to multiple IAV infections likely leads to the development of ADP that is cross-reactive to strains not previously encountered. Further analyses of the protective capacity of broadly reactive influenza-specific ADP is warranted.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Kilbourne, Ed" uniqKey="Kilbourne E">ED Kilbourne</name></author><author><name sortKey="Smith, C" uniqKey="Smith C">C Smith</name></author><author><name sortKey="Brett, I" uniqKey="Brett I">I Brett</name></author><author><name sortKey="Pokorny, Ba" uniqKey="Pokorny B">BA Pokorny</name></author><author><name sortKey="Johansson, B" uniqKey="Johansson B">B Johansson</name></author><author><name sortKey="Cox, N" uniqKey="Cox N">N Cox</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tricco, Ac" uniqKey="Tricco A">AC Tricco</name></author><author><name sortKey="Chit, A" uniqKey="Chit A">A Chit</name></author><author><name sortKey="Soobiah, C" uniqKey="Soobiah C">C Soobiah</name></author><author><name sortKey="Hallett, D" uniqKey="Hallett D">D Hallett</name></author><author><name sortKey="Meier, G" uniqKey="Meier G">G Meier</name></author><author><name sortKey="Chen, Mh" uniqKey="Chen M">MH Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Talbot, Hk" uniqKey="Talbot H">HK Talbot</name></author><author><name sortKey="Zhu, Y" uniqKey="Zhu Y">Y Zhu</name></author><author><name sortKey="Chen, Q" uniqKey="Chen Q">Q Chen</name></author><author><name sortKey="Williams, Jv" uniqKey="Williams J">JV Williams</name></author><author><name sortKey="Thompson, Mg" uniqKey="Thompson M">MG Thompson</name></author><author><name sortKey="Griffin, Mr" uniqKey="Griffin M">MR Griffin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Osterholm, Mt" uniqKey="Osterholm M">MT Osterholm</name></author><author><name sortKey="Kelley, Ns" uniqKey="Kelley N">NS Kelley</name></author><author><name sortKey="Sommer, A" uniqKey="Sommer A">A 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, CA USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27124730</article-id><article-id pub-id-type="pmc">4849649</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0154461</article-id><article-id pub-id-type="publisher-id">PONE-D-16-05243</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject><subj-group><subject>Organisms</subject><subj-group><subject>Animals</subject><subj-group><subject>Vertebrates</subject><subj-group><subject>Amniotes</subject><subj-group><subject>Mammals</subject><subj-group><subject>Primates</subject><subj-group><subject>Monkeys</subject><subj-group><subject>Old World monkeys</subject><subj-group><subject>Macaque</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Infectious Diseases</subject><subj-group><subject>Viral Diseases</subject><subj-group><subject>Influenza</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject><subj-group><subject>Organisms</subject><subj-group><subject>Viruses</subject><subj-group><subject>RNA viruses</subject><subj-group><subject>Orthomyxoviruses</subject><subj-group><subject>Influenza viruses</subject><subj-group><subject>Influenza A virus</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject><subj-group><subject>Microbiology</subject><subj-group><subject>Medical microbiology</subject><subj-group><subject>Microbial pathogens</subject><subj-group><subject>Viral pathogens</subject><subj-group><subject>Orthomyxoviruses</subject><subj-group><subject>Influenza viruses</subject><subj-group><subject>Influenza A virus</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and health sciences</subject><subj-group><subject>Pathology and laboratory medicine</subject><subj-group><subject>Pathogens</subject><subj-group><subject>Microbial pathogens</subject><subj-group><subject>Viral pathogens</subject><subj-group><subject>Orthomyxoviruses</subject><subj-group><subject>Influenza viruses</subject><subj-group><subject>Influenza A virus</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject><subj-group><subject>Organisms</subject><subj-group><subject>Viruses</subject><subj-group><subject>Viral pathogens</subject><subj-group><subject>Orthomyxoviruses</subject><subj-group><subject>Influenza viruses</subject><subj-group><subject>Influenza A virus</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject><subj-group><subject>Organisms</subject><subj-group><subject>Viruses</subject><subj-group><subject>RNA viruses</subject><subj-group><subject>Orthomyxoviruses</subject><subj-group><subject>Influenza viruses</subject><subj-group><subject>Influenza A virus</subject><subj-group><subject>H1N1</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject><subj-group><subject>Microbiology</subject><subj-group><subject>Medical microbiology</subject><subj-group><subject>Microbial pathogens</subject><subj-group><subject>Viral pathogens</subject><subj-group><subject>Orthomyxoviruses</subject><subj-group><subject>Influenza viruses</subject><subj-group><subject>Influenza A virus</subject><subj-group><subject>H1N1</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and health sciences</subject><subj-group><subject>Pathology and laboratory medicine</subject><subj-group><subject>Pathogens</subject><subj-group><subject>Microbial pathogens</subject><subj-group><subject>Viral pathogens</subject><subj-group><subject>Orthomyxoviruses</subject><subj-group><subject>Influenza viruses</subject><subj-group><subject>Influenza A virus</subject><subj-group><subject>H1N1</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject><subj-group><subject>Organisms</subject><subj-group><subject>Viruses</subject><subj-group><subject>Viral pathogens</subject><subj-group><subject>Orthomyxoviruses</subject><subj-group><subject>Influenza viruses</subject><subj-group><subject>Influenza A virus</subject><subj-group><subject>H1N1</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Physiology</subject><subj-group><subject>Immune Physiology</subject><subj-group><subject>Antibodies</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Physiology</subject><subj-group><subject>Immune Physiology</subject><subj-group><subject>Antibodies</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Immunology</subject><subj-group><subject>Immune System Proteins</subject><subj-group><subject>Antibodies</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Immunology</subject><subj-group><subject>Immune System Proteins</subject><subj-group><subject>Antibodies</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Biochemistry</subject><subj-group><subject>Proteins</subject><subj-group><subject>Immune System Proteins</subject><subj-group><subject>Antibodies</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Anatomy</subject><subj-group><subject>Body Fluids</subject><subj-group><subject>Blood</subject><subj-group><subject>Blood Plasma</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Anatomy</subject><subj-group><subject>Body Fluids</subject><subj-group><subject>Blood</subject><subj-group><subject>Blood Plasma</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Physiology</subject><subj-group><subject>Body Fluids</subject><subj-group><subject>Blood</subject><subj-group><subject>Blood Plasma</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Physiology</subject><subj-group><subject>Body Fluids</subject><subj-group><subject>Blood</subject><subj-group><subject>Blood Plasma</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Hematology</subject><subj-group><subject>Blood</subject><subj-group><subject>Blood Plasma</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Research and Analysis Methods</subject><subj-group><subject>Spectrum Analysis Techniques</subject><subj-group><subject>Spectrophotometry</subject><subj-group><subject>Cytophotometry</subject><subj-group><subject>Flow Cytometry</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Cell Biology</subject><subj-group><subject>Cell Processes</subject><subj-group><subject>Phagocytosis</subject></subj-group></subj-group></subj-group></subj-group></article-categories><title-group><article-title>Influenza-Specific Antibody-Dependent Phagocytosis</article-title><alt-title alt-title-type="running-head">ADP in Influenza</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Ana-Sosa-Batiz</surname><given-names>Fernanda</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Vanderven</surname><given-names>Hillary</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Jegaskanda</surname><given-names>Sinthujan</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Johnston</surname><given-names>Angus</given-names></name><xref ref-type="aff" rid="aff002"><sup>2</sup></xref><xref ref-type="aff" rid="aff003"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rockman</surname><given-names>Steven</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="aff" rid="aff004"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Laurie</surname><given-names>Karen</given-names></name><xref ref-type="aff" rid="aff005"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Barr</surname><given-names>Ian</given-names></name><xref ref-type="aff" rid="aff005"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Reading</surname><given-names>Patrick</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="aff" rid="aff005"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lichtfuss</surname><given-names>Marit</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kent</surname><given-names>Stephen J.</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="aff" rid="aff006"><sup>6</sup></xref><xref ref-type="aff" rid="aff007"><sup>7</sup></xref><xref ref-type="corresp" rid="cor001">*</xref></contrib></contrib-group><aff id="aff001"><label>1</label><addr-line>Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia</addr-line></aff><aff id="aff002"><label>2</label><addr-line>Drug Delivery, Disposition and Dynamics laboratory, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia</addr-line></aff><aff id="aff003"><label>3</label><addr-line>ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash University, Parkville, Australia</addr-line></aff><aff id="aff004"><label>4</label><addr-line>bioCSL Ltd, Parkville, Victoria, Australia</addr-line></aff><aff id="aff005"><label>5</label><addr-line>WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia</addr-line></aff><aff id="aff006"><label>6</label><addr-line>Melbourne Sexual Health Centre, Central Clinical School, Monash University, Melbourne, Australia</addr-line></aff><aff id="aff007"><label>7</label><addr-line>ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Parkville, Australia</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Krammer</surname><given-names>Florian</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>Icahn School of Medicine at Mount Sinai, UNITED STATES</addr-line></aff><author-notes><fn fn-type="COI-statement" id="coi001"><p><bold>Competing Interests: </bold>Dr. Steven Rockman is an employee of bioCSL Ltd, a subsidiary of CSL Ltd that manufactures IVIG. The remaining authors do not have a commercial or other association that might pose a conflict of interest. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.</p></fn><fn fn-type="con" id="contrib001"><p>Conceived and designed the experiments: SJK FA PR ML AJ. Performed the experiments: FA. Analyzed the data: FA HV SJ SR ML SJK. Contributed reagents/materials/analysis tools: AJ SR IB KL PR SJK. Wrote the paper: FA SJK. Commented and gave feedback on the manuscript: FA HV SJ AJ SR KL IB PR ML SJK.</p></fn><corresp id="cor001">* E-mail: <email>skent@unimelb.edu.au</email></corresp></author-notes><pub-date pub-type="epub"><day>28</day><month>4</month><year>2016</year></pub-date><pub-date pub-type="collection"><year>2016</year></pub-date><volume>11</volume><issue>4</issue><elocation-id>e0154461</elocation-id><history><date date-type="received"><day>14</day><month>2</month><year>2016</year></date><date date-type="accepted"><day>13</day><month>4</month><year>2016</year></date></history><permissions><copyright-statement>© 2016 Ana-Sosa-Batiz et al</copyright-statement><copyright-year>2016</copyright-year><copyright-holder>Ana-Sosa-Batiz et al</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="pone.0154461.pdf"></self-uri><abstract><sec id="sec001"><title>Background</title><p>Immunity to human influenza A virus (IAV) infection is only partially understood. Broadly non-neutralizing antibodies may assist in reducing disease but have not been well characterized.</p></sec><sec id="sec002"><title>Methods</title><p>We measured internalization of opsonized, influenza protein-coated fluorescent beads and live IAV into a monocytic cell line to study antibody-dependent phagocytosis (ADP) against multiple influenza hemagglutinin (HA) subtypes. We analyzed influenza HA-specific ADP in healthy human donors, in preparations of intravenous immunoglobulin (IVIG), and following IAV infection of humans and macaques.</p></sec><sec id="sec003"><title>Results</title><p>We found that both sera from healthy adults and IVIG preparations had broad ADP to multiple seasonal HA proteins and weak cross-reactive ADP to non-circulating HA proteins. The ADP in experimentally influenza-infected macaque plasma and naturally influenza-infected human sera mediated phagocytosis of both homologous and heterologous IAVs. Further, the IAV phagocytosed in an antibody-mediated manner had reduced infectivity <italic>in vitro</italic>.</p></sec><sec id="sec004"><title>Conclusion</title><p>We conclude that IAV infections in humans and macaques leads to the development of influenza-specific ADP that can clear IAV infection <italic>in vitro</italic>. Repeated exposure of humans to multiple IAV infections likely leads to the development of ADP that is cross-reactive to strains not previously encountered. Further analyses of the protective capacity of broadly reactive influenza-specific ADP is warranted.</p></sec></abstract><funding-group><award-group id="award001"><funding-source><institution>Australian National Health and Medical Research Council</institution></funding-source><award-id>628331</award-id><principal-award-recipient><name><surname>Kent</surname><given-names>Stephen J.</given-names></name></principal-award-recipient></award-group><award-group id="award002"><funding-source><institution>Australian National Health and Medical Research Council</institution></funding-source><award-id>1023294</award-id><principal-award-recipient><name><surname>Kent</surname><given-names>Stephen J.</given-names></name></principal-award-recipient></award-group><award-group id="award003"><funding-source><institution>Australian National Health and Medical Research Council</institution></funding-source><award-id>510488</award-id><principal-award-recipient><name><surname>Kent</surname><given-names>Stephen J.</given-names></name></principal-award-recipient></award-group><funding-statement>This work was supported by the Australian National Health and Medical Research Council [SJK 628331, 1023294, and 510488; <ext-link ext-link-type="uri" xlink:href="https://www.nhmrc.gov.au/">https://www.nhmrc.gov.au/</ext-link>]. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health [<ext-link ext-link-type="uri" xlink:href="http://www.health.gov.au/">http://www.health.gov.au/</ext-link>]. The funder provided support in the form of salaries for authors SJK, SJ, KL, IB, and PR, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.</funding-statement></funding-group><counts><fig-count count="7"></fig-count><table-count count="0"></table-count><page-count count="18"></page-count></counts><custom-meta-group><custom-meta id="data-availability"><meta-name>Data Availability</meta-name><meta-value>All relevant data are within the paper.</meta-value></custom-meta></custom-meta-group></article-meta><notes><title>Data Availability</title><p>All relevant data are within the paper.</p></notes></front></pmc><affiliations><list><country><li>Australie</li></country><region><li>Victoria (État)</li></region><settlement><li>Melbourne</li></settlement><orgName><li>Université de Melbourne</li></orgName></list><tree><country name="Australie"><region name="Victoria (État)"><name sortKey="Ana Sosa Batiz, Fernanda" sort="Ana Sosa Batiz, Fernanda" uniqKey="Ana Sosa Batiz F" first="Fernanda" last="Ana-Sosa-Batiz">Fernanda Ana-Sosa-Batiz</name></region><name sortKey="Barr, Ian" sort="Barr, Ian" uniqKey="Barr I" first="Ian" last="Barr">Ian Barr</name><name sortKey="Jegaskanda, Sinthujan" sort="Jegaskanda, Sinthujan" uniqKey="Jegaskanda S" first="Sinthujan" last="Jegaskanda">Sinthujan Jegaskanda</name><name sortKey="Johnston, Angus" sort="Johnston, Angus" uniqKey="Johnston A" first="Angus" last="Johnston">Angus Johnston</name><name sortKey="Johnston, Angus" sort="Johnston, Angus" uniqKey="Johnston A" first="Angus" last="Johnston">Angus Johnston</name><name sortKey="Kent, Stephen J" sort="Kent, Stephen J" uniqKey="Kent S" first="Stephen J." last="Kent">Stephen J. Kent</name><name sortKey="Kent, Stephen J" sort="Kent, Stephen J" uniqKey="Kent S" first="Stephen J." last="Kent">Stephen J. Kent</name><name sortKey="Kent, Stephen J" sort="Kent, Stephen J" uniqKey="Kent S" first="Stephen J." last="Kent">Stephen J. Kent</name><name sortKey="Laurie, Karen" sort="Laurie, Karen" uniqKey="Laurie K" first="Karen" last="Laurie">Karen Laurie</name><name sortKey="Lichtfuss, Marit" sort="Lichtfuss, Marit" uniqKey="Lichtfuss M" first="Marit" last="Lichtfuss">Marit Lichtfuss</name><name sortKey="Reading, Patrick" sort="Reading, Patrick" uniqKey="Reading P" first="Patrick" last="Reading">Patrick Reading</name><name sortKey="Reading, Patrick" sort="Reading, Patrick" uniqKey="Reading P" first="Patrick" last="Reading">Patrick Reading</name><name sortKey="Rockman, Steven" sort="Rockman, Steven" uniqKey="Rockman S" first="Steven" last="Rockman">Steven Rockman</name><name sortKey="Rockman, Steven" sort="Rockman, Steven" uniqKey="Rockman S" first="Steven" last="Rockman">Steven Rockman</name><name sortKey="Vanderven, Hillary" sort="Vanderven, Hillary" uniqKey="Vanderven H" first="Hillary" last="Vanderven">Hillary Vanderven</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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