Protection against maternal infection-associated fetal growth restriction: proof-of-concept with a microbial-derived immunomodulator.
Identifieur interne : 000341 ( PubMed/Corpus ); précédent : 000340; suivant : 000342Protection against maternal infection-associated fetal growth restriction: proof-of-concept with a microbial-derived immunomodulator.
Auteurs : N M Scott ; J F Lauzon-Joset ; A C Jones ; K T Mincham ; N M Troy ; J. Leffler ; M. Serralha ; S L Prescott ; S A Robertson ; C. Pasquali ; A. Bosco ; P G Holt ; D H StricklandSource :
- Mucosal immunology [ 1935-3456 ] ; 2017.
English descriptors
- KwdEn :
- Abortion, Spontaneous (etiology), Abortion, Spontaneous (immunology), Abortion, Spontaneous (prevention & control), Animals, Antigens, Bacterial (immunology), Bacterial Infections (complications), Bacterial Infections (immunology), Disease Models, Animal, Down-Regulation, Female, Fetal Development, Humans, Immunologic Factors (immunology), Inflammation Mediators (metabolism), Influenza A virus (immunology), Lipopolysaccharides (immunology), Male, Mice, Mice, Inbred BALB C, Orthomyxoviridae Infections (complications), Orthomyxoviridae Infections (immunology), Pregnancy, Prenatal Exposure Delayed Effects (immunology), Prenatal Exposure Delayed Effects (prevention & control), Proof of Concept Study.
- MESH :
- chemical , immunology : Antigens, Bacterial, Immunologic Factors, Lipopolysaccharides.
- complications : Bacterial Infections, Orthomyxoviridae Infections.
- etiology : Abortion, Spontaneous.
- immunology : Abortion, Spontaneous, Bacterial Infections, Influenza A virus, Orthomyxoviridae Infections, Prenatal Exposure Delayed Effects.
- chemical , metabolism : Inflammation Mediators.
- prevention & control : Abortion, Spontaneous, Prenatal Exposure Delayed Effects.
- Animals, Disease Models, Animal, Down-Regulation, Female, Fetal Development, Humans, Male, Mice, Mice, Inbred BALB C, Pregnancy, Proof of Concept Study.
Abstract
Infection-associated inflammatory stress during pregnancy is the most common cause of fetal growth restriction and/or miscarriage. Treatment strategies for protection of at-risk mothers are limited to a narrow range of vaccines, which do not cover the bulk of the common pathogens most frequently encountered. Using mouse models, we demonstrate that oral treatment during pregnancy with a microbial-derived immunomodulator (OM85), currently used clinically for attenuation of infection-associated airway inflammatory symptoms in infants-adults, markedly reduces risk for fetal loss/growth restriction resulting from maternal challenge with bacterial lipopolysaccharide or influenza. Focusing on LPS exposure, we demonstrate that the key molecular indices of maternal inflammatory stress, notably high levels of RANTES, MIP-1α, CCL2, KC, and G-CSF (granulocyte colony-stimulating factor) in gestational tissues/serum, are abrogated by OM85 pretreatment. Systems-level analyses conducted in parallel using RNASeq revealed that OM85 pretreatment selectively tunes LPS-induced activation in maternal gestational tissues for attenuated expression of TNF, IL1, and IFNG-driven proinflammatory networks, without constraining Type1-IFN-associated networks central to first-line antimicrobial defense. This study suggests that broad-spectrum protection-of-pregnancy against infection-associated inflammatory stress, without compromising capacity for efficient pathogen eradication, represents an achievable therapeutic goal.
DOI: 10.1038/mi.2016.85
PubMed: 27759021
Links to Exploration step
pubmed:27759021Le document en format XML
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Bosco</name><affiliation><nlm:affiliation>Telethon Kids Institute, The University of Western Australia, West Perth, Western Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Holt, P G" sort="Holt, P G" uniqKey="Holt P" first="P G" last="Holt">P G Holt</name><affiliation><nlm:affiliation>Telethon Kids Institute, The University of Western Australia, West Perth, Western Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Strickland, D H" sort="Strickland, D H" uniqKey="Strickland D" first="D H" last="Strickland">D H Strickland</name><affiliation><nlm:affiliation>Telethon Kids Institute, The University of Western Australia, West Perth, Western Australia, Australia.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:27759021</idno><idno type="pmid">27759021</idno><idno type="doi">10.1038/mi.2016.85</idno><idno type="wicri:Area/PubMed/Corpus">000341</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000341</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Protection against maternal infection-associated fetal growth restriction: proof-of-concept with a microbial-derived immunomodulator.</title><author><name sortKey="Scott, N M" sort="Scott, N M" uniqKey="Scott N" first="N M" last="Scott">N M Scott</name><affiliation><nlm:affiliation>Telethon Kids Institute, The University of Western Australia, West Perth, Western Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Lauzon Joset, J F" sort="Lauzon Joset, J F" uniqKey="Lauzon Joset J" first="J F" last="Lauzon-Joset">J F Lauzon-Joset</name><affiliation><nlm:affiliation>Telethon Kids Institute, The University of Western Australia, West Perth, Western Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Jones, A C" sort="Jones, A C" uniqKey="Jones A" first="A C" last="Jones">A C Jones</name><affiliation><nlm:affiliation>Telethon Kids Institute, The University of Western Australia, West Perth, Western Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Mincham, K T" sort="Mincham, K T" uniqKey="Mincham K" first="K T" last="Mincham">K T Mincham</name><affiliation><nlm:affiliation>Telethon Kids Institute, The University of Western Australia, West Perth, Western Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Troy, N M" sort="Troy, N M" uniqKey="Troy N" first="N M" last="Troy">N M Troy</name><affiliation><nlm:affiliation>Telethon Kids Institute, The University of Western Australia, West Perth, Western Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Leffler, J" sort="Leffler, J" uniqKey="Leffler J" first="J" last="Leffler">J. Leffler</name><affiliation><nlm:affiliation>Telethon Kids Institute, The University of Western Australia, West Perth, Western Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Serralha, M" sort="Serralha, M" uniqKey="Serralha M" first="M" last="Serralha">M. Serralha</name><affiliation><nlm:affiliation>Telethon Kids Institute, The University of Western Australia, West Perth, Western Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Prescott, S L" sort="Prescott, S L" uniqKey="Prescott S" first="S L" last="Prescott">S L Prescott</name><affiliation><nlm:affiliation>Telethon Kids Institute, The University of Western Australia, West Perth, Western Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Robertson, S A" sort="Robertson, S A" uniqKey="Robertson S" first="S A" last="Robertson">S A Robertson</name><affiliation><nlm:affiliation>Robinson Research Institute and School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Pasquali, C" sort="Pasquali, C" uniqKey="Pasquali C" first="C" last="Pasquali">C. Pasquali</name><affiliation><nlm:affiliation>OM Pharma, SA Geneva, Geneva, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Bosco, A" sort="Bosco, A" uniqKey="Bosco A" first="A" last="Bosco">A. Bosco</name><affiliation><nlm:affiliation>Telethon Kids Institute, The University of Western Australia, West Perth, Western Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Holt, P G" sort="Holt, P G" uniqKey="Holt P" first="P G" last="Holt">P G Holt</name><affiliation><nlm:affiliation>Telethon Kids Institute, The University of Western Australia, West Perth, Western Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Strickland, D H" sort="Strickland, D H" uniqKey="Strickland D" first="D H" last="Strickland">D H Strickland</name><affiliation><nlm:affiliation>Telethon Kids Institute, The University of Western Australia, West Perth, Western Australia, Australia.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Mucosal immunology</title><idno type="eISSN">1935-3456</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Abortion, Spontaneous (etiology)</term><term>Abortion, Spontaneous (immunology)</term><term>Abortion, Spontaneous (prevention & control)</term><term>Animals</term><term>Antigens, Bacterial (immunology)</term><term>Bacterial Infections (complications)</term><term>Bacterial Infections (immunology)</term><term>Disease Models, Animal</term><term>Down-Regulation</term><term>Female</term><term>Fetal Development</term><term>Humans</term><term>Immunologic Factors (immunology)</term><term>Inflammation Mediators (metabolism)</term><term>Influenza A virus (immunology)</term><term>Lipopolysaccharides (immunology)</term><term>Male</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Orthomyxoviridae Infections (complications)</term><term>Orthomyxoviridae Infections (immunology)</term><term>Pregnancy</term><term>Prenatal Exposure Delayed Effects (immunology)</term><term>Prenatal Exposure Delayed Effects (prevention & control)</term><term>Proof of Concept Study</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antigens, Bacterial</term><term>Immunologic Factors</term><term>Lipopolysaccharides</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Bacterial Infections</term><term>Orthomyxoviridae Infections</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Abortion, Spontaneous</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Abortion, Spontaneous</term><term>Bacterial Infections</term><term>Influenza A virus</term><term>Orthomyxoviridae Infections</term><term>Prenatal Exposure Delayed Effects</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Inflammation Mediators</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Abortion, Spontaneous</term><term>Prenatal Exposure Delayed Effects</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Down-Regulation</term><term>Female</term><term>Fetal Development</term><term>Humans</term><term>Male</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Pregnancy</term><term>Proof of Concept Study</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Infection-associated inflammatory stress during pregnancy is the most common cause of fetal growth restriction and/or miscarriage. Treatment strategies for protection of at-risk mothers are limited to a narrow range of vaccines, which do not cover the bulk of the common pathogens most frequently encountered. Using mouse models, we demonstrate that oral treatment during pregnancy with a microbial-derived immunomodulator (OM85), currently used clinically for attenuation of infection-associated airway inflammatory symptoms in infants-adults, markedly reduces risk for fetal loss/growth restriction resulting from maternal challenge with bacterial lipopolysaccharide or influenza. Focusing on LPS exposure, we demonstrate that the key molecular indices of maternal inflammatory stress, notably high levels of RANTES, MIP-1α, CCL2, KC, and G-CSF (granulocyte colony-stimulating factor) in gestational tissues/serum, are abrogated by OM85 pretreatment. Systems-level analyses conducted in parallel using RNASeq revealed that OM85 pretreatment selectively tunes LPS-induced activation in maternal gestational tissues for attenuated expression of TNF, IL1, and IFNG-driven proinflammatory networks, without constraining Type1-IFN-associated networks central to first-line antimicrobial defense. This study suggests that broad-spectrum protection-of-pregnancy against infection-associated inflammatory stress, without compromising capacity for efficient pathogen eradication, represents an achievable therapeutic goal.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27759021</PMID><DateCompleted><Year>2018</Year><Month>01</Month><Day>23</Day></DateCompleted><DateRevised><Year>2018</Year><Month>03</Month><Day>16</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1935-3456</ISSN><JournalIssue CitedMedium="Internet"><Volume>10</Volume><Issue>3</Issue><PubDate><Year>2017</Year><Month>05</Month></PubDate></JournalIssue><Title>Mucosal immunology</Title><ISOAbbreviation>Mucosal Immunol</ISOAbbreviation></Journal><ArticleTitle>Protection against maternal infection-associated fetal growth restriction: proof-of-concept with a microbial-derived immunomodulator.</ArticleTitle><Pagination><MedlinePgn>789-801</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/mi.2016.85</ELocationID><Abstract><AbstractText>Infection-associated inflammatory stress during pregnancy is the most common cause of fetal growth restriction and/or miscarriage. Treatment strategies for protection of at-risk mothers are limited to a narrow range of vaccines, which do not cover the bulk of the common pathogens most frequently encountered. Using mouse models, we demonstrate that oral treatment during pregnancy with a microbial-derived immunomodulator (OM85), currently used clinically for attenuation of infection-associated airway inflammatory symptoms in infants-adults, markedly reduces risk for fetal loss/growth restriction resulting from maternal challenge with bacterial lipopolysaccharide or influenza. Focusing on LPS exposure, we demonstrate that the key molecular indices of maternal inflammatory stress, notably high levels of RANTES, MIP-1α, CCL2, KC, and G-CSF (granulocyte colony-stimulating factor) in gestational tissues/serum, are abrogated by OM85 pretreatment. Systems-level analyses conducted in parallel using RNASeq revealed that OM85 pretreatment selectively tunes LPS-induced activation in maternal gestational tissues for attenuated expression of TNF, IL1, and IFNG-driven proinflammatory networks, without constraining Type1-IFN-associated networks central to first-line antimicrobial defense. This study suggests that broad-spectrum protection-of-pregnancy against infection-associated inflammatory stress, without compromising capacity for efficient pathogen eradication, represents an achievable therapeutic goal.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Scott</LastName><ForeName>N M</ForeName><Initials>NM</Initials><AffiliationInfo><Affiliation>Telethon Kids Institute, The University of Western Australia, West Perth, Western Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lauzon-Joset</LastName><ForeName>J F</ForeName><Initials>JF</Initials><AffiliationInfo><Affiliation>Telethon Kids Institute, The University of Western Australia, West Perth, Western Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jones</LastName><ForeName>A C</ForeName><Initials>AC</Initials><AffiliationInfo><Affiliation>Telethon Kids Institute, The University of Western Australia, West Perth, Western Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mincham</LastName><ForeName>K T</ForeName><Initials>KT</Initials><AffiliationInfo><Affiliation>Telethon Kids Institute, The University of Western Australia, West Perth, Western Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Troy</LastName><ForeName>N M</ForeName><Initials>NM</Initials><AffiliationInfo><Affiliation>Telethon Kids Institute, The University of Western Australia, West Perth, Western Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Leffler</LastName><ForeName>J</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Telethon Kids Institute, The University of Western Australia, West Perth, Western Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Serralha</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Telethon Kids Institute, The University of Western Australia, West Perth, Western Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Prescott</LastName><ForeName>S L</ForeName><Initials>SL</Initials><AffiliationInfo><Affiliation>Telethon Kids Institute, The University of Western Australia, West Perth, Western Australia, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>School of Paediatrics and Child Health, The University of Western Australia, West Perth, Western Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Robertson</LastName><ForeName>S A</ForeName><Initials>SA</Initials><AffiliationInfo><Affiliation>Robinson Research Institute and School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pasquali</LastName><ForeName>C</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>OM Pharma, SA Geneva, Geneva, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bosco</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Telethon Kids Institute, The University of Western Australia, West Perth, Western Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Holt</LastName><ForeName>P G</ForeName><Initials>PG</Initials><AffiliationInfo><Affiliation>Telethon Kids Institute, The University of Western Australia, West Perth, Western Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Strickland</LastName><ForeName>D H</ForeName><Initials>DH</Initials><AffiliationInfo><Affiliation>Telethon Kids Institute, The University of Western Australia, West Perth, Western Australia, Australia.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>10</Month><Day>19</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Mucosal Immunol</MedlineTA><NlmUniqueID>101299742</NlmUniqueID><ISSNLinking>1933-0219</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000942">Antigens, Bacterial</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007155">Immunologic Factors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018836">Inflammation Mediators</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D008070">Lipopolysaccharides</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000022" MajorTopicYN="N">Abortion, Spontaneous</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="N">etiology</QualifierName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000517" MajorTopicYN="N">prevention & control</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000942" MajorTopicYN="N">Antigens, Bacterial</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001424" MajorTopicYN="N">Bacterial Infections</DescriptorName><QualifierName UI="Q000150" 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MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009980" MajorTopicYN="N">Influenza A virus</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008070" MajorTopicYN="N">Lipopolysaccharides</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008807" MajorTopicYN="N">Mice, Inbred BALB C</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009976" MajorTopicYN="N">Orthomyxoviridae Infections</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011247" MajorTopicYN="N">Pregnancy</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011297" MajorTopicYN="N">Prenatal Exposure Delayed Effects</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000517" MajorTopicYN="N">prevention & control</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000075082" MajorTopicYN="N">Proof of Concept Study</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>05</Month><Day>21</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>08</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2016</Year><Month>10</Month><Day>21</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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