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Elevated Adaptive Immune Responses Are Associated with Latent Infections of Wuchereria bancrofti

Identifieur interne : 004338 ( Main/Exploration ); précédent : 004337; suivant : 004339

Elevated Adaptive Immune Responses Are Associated with Latent Infections of Wuchereria bancrofti

Auteurs : Kathrin Arndts [Allemagne] ; Susanne Deininger [Allemagne] ; Sabine Specht [Allemagne] ; Ute Klarmann [Allemagne] ; Sabine Mand [Allemagne] ; Tomabu Adjobimey [Allemagne] ; Alexander Y. Debrah [Ghana] ; Linda Batsa [Ghana] ; Alexander Kwarteng [Ghana] ; Christian Epp [Allemagne] ; Mark Taylor [Royaume-Uni] ; Ohene Adjei [Ghana] ; Laura E. Layland [Allemagne] ; Achim Hoerauf [Allemagne]

Source :

RBID : PMC:3317915

Descripteurs français

English descriptors

Abstract

In order to guarantee the fulfillment of their complex lifecycle, adult filarial nematodes release millions of microfilariae (MF), which are taken up by mosquito vectors. The current strategy to eliminate lymphatic filariasis as a public health problem focuses upon interrupting this transmission through annual mass drug administration (MDA). It remains unclear however, how many rounds of MDA are required to achieve low enough levels of MF to cease transmission. Interestingly, with the development of further diagnostic tools a relatively neglected cohort of asymptomatic (non-lymphedema) amicrofilaremic (latent) individuals has become apparent. Indeed, epidemiological studies have suggested that there are equal numbers of patent (MF+) and latent individuals. Since the latter represent a roadblock for transmission, we studied differences in immune responses of infected asymptomatic male individuals (n = 159) presenting either patent (n = 92 MF+) or latent (n = 67 MF) manifestations of Wuchereria bancrofti. These individuals were selected on the basis of MF, circulating filarial antigen in plasma and detectable worm nests. Immunological profiles of either Th1/Th17, Th2, regulatory or innate responses were determined after stimulation of freshly isolated PBMCs with either filarial-specific extract or bystander stimuli. In addition, levels of total and filarial-specific antibodies, both IgG subclasses and IgE, were ascertained from plasma. Results from these individuals were compared with those from 22 healthy volunteers from the same endemic area. Interestingly, we observed that in contrast to MF+ patients, latent infected individuals had lower numbers of worm nests and increased adaptive immune responses including antigen-specific IL-5. These data highlight the immunosuppressive status of MF+ individuals, regardless of age or clinical hydrocele and reveal immunological profiles associated with latency and immune-mediated suppression of parasite transmission.


Url:
DOI: 10.1371/journal.pntd.0001611
PubMed: 22509424
PubMed Central: 3317915


Affiliations:


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Le document en format XML

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</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department für Infektiologie, Parasitologie, Universitätsklinikum Heidelberg, Heidelberg</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Taylor, Mark" sort="Taylor, Mark" uniqKey="Taylor M" first="Mark" last="Taylor">Mark Taylor</name>
<affiliation wicri:level="1">
<nlm:aff id="aff6">
<addr-line>Liverpool School of Tropical Medicine, Liverpool, United Kingdom</addr-line>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Liverpool School of Tropical Medicine, Liverpool</wicri:regionArea>
<wicri:noRegion>Liverpool</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Adjei, Ohene" sort="Adjei, Ohene" uniqKey="Adjei O" first="Ohene" last="Adjei">Ohene Adjei</name>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<addr-line>Kumasi Centre for Collaborative Research in Tropical Medicine, Kumasi, Ghana</addr-line>
</nlm:aff>
<country xml:lang="fr">Ghana</country>
<wicri:regionArea>Kumasi Centre for Collaborative Research in Tropical Medicine, Kumasi</wicri:regionArea>
<wicri:noRegion>Kumasi</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<addr-line>Faculty of Allied Health Sciences, Department of Theoretical and Applied Biology, and School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana</addr-line>
</nlm:aff>
<country xml:lang="fr">Ghana</country>
<wicri:regionArea>Faculty of Allied Health Sciences, Department of Theoretical and Applied Biology, and School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi</wicri:regionArea>
<wicri:noRegion>Kumasi</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Layland, Laura E" sort="Layland, Laura E" uniqKey="Layland L" first="Laura E." last="Layland">Laura E. Layland</name>
<affiliation wicri:level="3">
<nlm:aff id="aff1">
<addr-line>Institute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Hoerauf, Achim" sort="Hoerauf, Achim" uniqKey="Hoerauf A" first="Achim" last="Hoerauf">Achim Hoerauf</name>
<affiliation wicri:level="3">
<nlm:aff id="aff1">
<addr-line>Institute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series>
<title level="j">PLoS Neglected Tropical Diseases</title>
<idno type="ISSN">1935-2727</idno>
<idno type="eISSN">1935-2735</idno>
<imprint>
<date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Adolescent</term>
<term>Adult</term>
<term>Animals</term>
<term>Antibodies, Helminth (blood)</term>
<term>Asymptomatic Infections</term>
<term>Cohort Studies</term>
<term>Elephantiasis, Filarial (immunology)</term>
<term>Elephantiasis, Filarial (pathology)</term>
<term>Humans</term>
<term>Immunoglobulin E (blood)</term>
<term>Immunoglobulin G (blood)</term>
<term>Leukocytes, Mononuclear (immunology)</term>
<term>Male</term>
<term>Middle Aged</term>
<term>T-Lymphocytes (immunology)</term>
<term>Wuchereria bancrofti (immunology)</term>
<term>Wuchereria bancrofti (pathogenicity)</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Adolescent</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Agranulocytes (immunologie)</term>
<term>Animaux</term>
<term>Anticorps antihelminthe (sang)</term>
<term>Filariose lymphatique (anatomopathologie)</term>
<term>Filariose lymphatique (immunologie)</term>
<term>Humains</term>
<term>Immunoglobuline E (sang)</term>
<term>Immunoglobuline G (sang)</term>
<term>Infections asymptomatiques</term>
<term>Jeune adulte</term>
<term>Lymphocytes T (immunologie)</term>
<term>Mâle</term>
<term>Wuchereria bancrofti (immunologie)</term>
<term>Wuchereria bancrofti (pathogénicité)</term>
<term>Études de cohortes</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en">
<term>Antibodies, Helminth</term>
<term>Immunoglobulin E</term>
<term>Immunoglobulin G</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr">
<term>Filariose lymphatique</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<term>Agranulocytes</term>
<term>Filariose lymphatique</term>
<term>Lymphocytes T</term>
<term>Wuchereria bancrofti</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en">
<term>Elephantiasis, Filarial</term>
<term>Leukocytes, Mononuclear</term>
<term>T-Lymphocytes</term>
<term>Wuchereria bancrofti</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en">
<term>Wuchereria bancrofti</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr">
<term>Wuchereria bancrofti</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en">
<term>Elephantiasis, Filarial</term>
</keywords>
<keywords scheme="MESH" qualifier="sang" xml:lang="fr">
<term>Anticorps antihelminthe</term>
<term>Immunoglobuline E</term>
<term>Immunoglobuline G</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Adolescent</term>
<term>Adult</term>
<term>Animals</term>
<term>Asymptomatic Infections</term>
<term>Cohort Studies</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Adolescent</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Animaux</term>
<term>Humains</term>
<term>Infections asymptomatiques</term>
<term>Jeune adulte</term>
<term>Mâle</term>
<term>Études de cohortes</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>In order to guarantee the fulfillment of their complex lifecycle, adult filarial nematodes release millions of microfilariae (MF), which are taken up by mosquito vectors. The current strategy to eliminate lymphatic filariasis as a public health problem focuses upon interrupting this transmission through annual mass drug administration (MDA). It remains unclear however, how many rounds of MDA are required to achieve low enough levels of MF to cease transmission. Interestingly, with the development of further diagnostic tools a relatively neglected cohort of asymptomatic (non-lymphedema) amicrofilaremic (latent) individuals has become apparent. Indeed, epidemiological studies have suggested that there are equal numbers of patent (MF
<sup>+</sup>
) and latent individuals. Since the latter represent a roadblock for transmission, we studied differences in immune responses of infected asymptomatic male individuals (n = 159) presenting either patent (n = 92 MF
<sup>+</sup>
) or latent (n = 67 MF
<sup></sup>
) manifestations of
<italic>Wuchereria bancrofti</italic>
. These individuals were selected on the basis of MF, circulating filarial antigen in plasma and detectable worm nests. Immunological profiles of either Th1/Th17, Th2, regulatory or innate responses were determined after stimulation of freshly isolated PBMCs with either filarial-specific extract or bystander stimuli. In addition, levels of total and filarial-specific antibodies, both IgG subclasses and IgE, were ascertained from plasma. Results from these individuals were compared with those from 22 healthy volunteers from the same endemic area. Interestingly, we observed that in contrast to MF
<sup>+</sup>
patients, latent infected individuals had lower numbers of worm nests and increased adaptive immune responses including antigen-specific IL-5. These data highlight the immunosuppressive status of MF
<sup>+</sup>
individuals, regardless of age or clinical hydrocele and reveal immunological profiles associated with latency and immune-mediated suppression of parasite transmission.</p>
</div>
</front>
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