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Humans from Wuchereria bancrofti endemic area elicit substantial immune response to proteins of the filarial parasite Brugia malayi and its endosymbiont Wolbachia

Identifieur interne : 000512 ( Main/Exploration ); précédent : 000511; suivant : 000513

Humans from Wuchereria bancrofti endemic area elicit substantial immune response to proteins of the filarial parasite Brugia malayi and its endosymbiont Wolbachia

Auteurs : Ruchi Jha ; Mamta Gangwar ; Dhanvantri Chahar [Inde] ; Anand Setty Balakrishnan [États-Unis] ; Mahendra Pal Singh Negi ; Shailja Misra-Bhattacharya [Inde]

Source :

RBID : PMC:5259955

Descripteurs français

English descriptors

Abstract

Background

In the past, immune responses to several Brugia malayi immunodominant antigens have been characterized in filaria-infected populations; however, little is known regarding Wolbachia proteins. We earlier cloned and characterized few B. malayi (trehalose-6-phosphate phosphatase, Bm-TPP and heavy chain myosin, BmAF-Myo) and Wolbachia (translation initiation factor-1, Wol Tl IF-1 and NAD+-dependent DNA ligase, wBm-LigA) proteins and investigated the immune responses, which they triggered in animal models. The current study emphasizes on immunological characteristics of these proteins in three major categories of filarial endemic zones: endemic normal (EN, asymptomatic, amicrofilaraemic; putatively immune), microfilariae carriers (MF, asymptomatic but microfilaraemic), and chronic filarial patients (CP, symptomatic and mostly amicrofilaraemic).

Methods

Immunoblotting and ELISA were carried out to measure IgG and isotype antibodies against these recombinant proteins in various clinical categories. Involvement of serum antibodies in infective larvae killing was assessed by antibody-dependent cellular adhesion and cytotoxicity assay. Cellular immune response was investigated by in vitro proliferation of peripheral blood mononuclear cells (PBMCs) and reactive oxygen species (ROS) generation in these cells after stimulation.

Results

Immune responses of EN and CP displayed almost similar level of IgG to Wol Tl IF-1 while other three proteins had higher serum IgG in EN individuals only. Specific IgA, IgG1, IgG3 and IgM to Bm-TPP were high in EN subjects, while BmAF-Myo additionally showed elevated IgG2. Enhanced IgA and IgG3 were detected in both EN and CP individuals in response to Wol Tl IF-1 antigen, but IgG1 and IgM were high only in EN individuals. wBm-LigA and BmAF-Myo exhibited almost similar pattern of antibody responses. PBMC isolated from EN subjects exhibited higher proliferation and ROS generation when stimulated with all three proteins except for Wol Tl IF-1.

Conclusions

Overall, these findings display high immunogenicity of all four proteins in human subjects and revealed that the EN population was exposed to both B. malayi and Wolbachia proteins simultaneously. In addition, immune responses to Wol Tl IF-1 suggest possible role of this factor in Wolbachia-induced pathological responses while immune responses to other three proteins suggest that these can be explored further as vaccine candidates.

Electronic supplementary material

The online version of this article (doi:10.1186/s13071-016-1963-x) contains supplementary material, which is available to authorized users.


Url:
DOI: 10.1186/s13071-016-1963-x
PubMed: 28118850
PubMed Central: 5259955


Affiliations:


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Le document en format XML

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BS 10/1, Sector 10 Jankipuram Extension, Sitapur Road, Lucknow, UP 226031 India</nlm:aff>
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<term>Animals</term>
<term>Antibodies, Bacterial (analysis)</term>
<term>Antibodies, Bacterial (immunology)</term>
<term>Antibodies, Helminth (analysis)</term>
<term>Antibodies, Helminth (immunology)</term>
<term>Bacterial Proteins (analysis)</term>
<term>Bacterial Proteins (immunology)</term>
<term>Brugia malayi (genetics)</term>
<term>Brugia malayi (immunology)</term>
<term>Brugia malayi (microbiology)</term>
<term>Elephantiasis, Filarial (immunology)</term>
<term>Elephantiasis, Filarial (parasitology)</term>
<term>Enzyme-Linked Immunosorbent Assay</term>
<term>Female</term>
<term>Filariasis (immunology)</term>
<term>Filariasis (parasitology)</term>
<term>Helminth Proteins (analysis)</term>
<term>Helminth Proteins (immunology)</term>
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<term>Immunity, Humoral</term>
<term>Immunoblotting</term>
<term>Leukocytes, Mononuclear (immunology)</term>
<term>Leukocytes, Mononuclear (parasitology)</term>
<term>Symbiosis</term>
<term>Wolbachia (immunology)</term>
<term>Wolbachia (physiology)</term>
<term>Wuchereria bancrofti (genetics)</term>
<term>Wuchereria bancrofti (immunology)</term>
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<term>Agranulocytes (immunologie)</term>
<term>Agranulocytes (parasitologie)</term>
<term>Animaux</term>
<term>Anticorps antibactériens (analyse)</term>
<term>Anticorps antibactériens (immunologie)</term>
<term>Anticorps antihelminthe (analyse)</term>
<term>Anticorps antihelminthe (immunologie)</term>
<term>Brugia malayi (génétique)</term>
<term>Brugia malayi (immunologie)</term>
<term>Brugia malayi (microbiologie)</term>
<term>Femelle</term>
<term>Filariose lymphatique (immunologie)</term>
<term>Filariose lymphatique (parasitologie)</term>
<term>Filarioses (immunologie)</term>
<term>Filarioses (parasitologie)</term>
<term>Humains</term>
<term>Immunité humorale</term>
<term>Immunotransfert</term>
<term>Protéines bactériennes (analyse)</term>
<term>Protéines bactériennes (immunologie)</term>
<term>Protéines d'helminthes (analyse)</term>
<term>Protéines d'helminthes (immunologie)</term>
<term>Symbiose</term>
<term>Test ELISA</term>
<term>Wolbachia (immunologie)</term>
<term>Wolbachia (physiologie)</term>
<term>Wuchereria bancrofti (génétique)</term>
<term>Wuchereria bancrofti (immunologie)</term>
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<term>Antibodies, Bacterial</term>
<term>Antibodies, Helminth</term>
<term>Bacterial Proteins</term>
<term>Helminth Proteins</term>
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<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en">
<term>Antibodies, Bacterial</term>
<term>Antibodies, Helminth</term>
<term>Bacterial Proteins</term>
<term>Helminth Proteins</term>
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<keywords scheme="MESH" qualifier="analyse" xml:lang="fr">
<term>Anticorps antibactériens</term>
<term>Anticorps antihelminthe</term>
<term>Protéines bactériennes</term>
<term>Protéines d'helminthes</term>
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<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Brugia malayi</term>
<term>Wuchereria bancrofti</term>
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<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Brugia malayi</term>
<term>Wuchereria bancrofti</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<term>Agranulocytes</term>
<term>Anticorps antibactériens</term>
<term>Anticorps antihelminthe</term>
<term>Brugia malayi</term>
<term>Filariose lymphatique</term>
<term>Filarioses</term>
<term>Protéines bactériennes</term>
<term>Protéines d'helminthes</term>
<term>Wolbachia</term>
<term>Wuchereria bancrofti</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en">
<term>Brugia malayi</term>
<term>Elephantiasis, Filarial</term>
<term>Filariasis</term>
<term>Leukocytes, Mononuclear</term>
<term>Wolbachia</term>
<term>Wuchereria bancrofti</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiologie" xml:lang="fr">
<term>Brugia malayi</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiology" xml:lang="en">
<term>Brugia malayi</term>
</keywords>
<keywords scheme="MESH" qualifier="parasitologie" xml:lang="fr">
<term>Agranulocytes</term>
<term>Filariose lymphatique</term>
<term>Filarioses</term>
</keywords>
<keywords scheme="MESH" qualifier="parasitology" xml:lang="en">
<term>Elephantiasis, Filarial</term>
<term>Filariasis</term>
<term>Leukocytes, Mononuclear</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr">
<term>Wolbachia</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en">
<term>Wolbachia</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Animals</term>
<term>Enzyme-Linked Immunosorbent Assay</term>
<term>Female</term>
<term>Humans</term>
<term>Immunity, Humoral</term>
<term>Immunoblotting</term>
<term>Symbiosis</term>
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<term>Animaux</term>
<term>Femelle</term>
<term>Humains</term>
<term>Immunité humorale</term>
<term>Immunotransfert</term>
<term>Symbiose</term>
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<front>
<div type="abstract" xml:lang="en">
<sec>
<title>Background</title>
<p>In the past, immune responses to several
<italic>Brugia malayi</italic>
immunodominant antigens have been characterized in filaria-infected populations; however, little is known regarding
<italic>Wolbachia</italic>
proteins. We earlier cloned and characterized few
<italic>B. malayi</italic>
(trehalose-6-phosphate phosphatase, Bm-TPP and heavy chain myosin, BmAF-Myo) and
<italic>Wolbachia</italic>
(translation initiation factor-1, Wol Tl IF-1 and NAD
<sup>+</sup>
-dependent DNA ligase,
<italic>w</italic>
Bm-LigA) proteins and investigated the immune responses, which they triggered in animal models. The current study emphasizes on immunological characteristics of these proteins in three major categories of filarial endemic zones: endemic normal (EN, asymptomatic, amicrofilaraemic; putatively immune), microfilariae carriers (MF, asymptomatic but microfilaraemic), and chronic filarial patients (CP, symptomatic and mostly amicrofilaraemic).</p>
</sec>
<sec>
<title>Methods</title>
<p>Immunoblotting and ELISA were carried out to measure IgG and isotype antibodies against these recombinant proteins in various clinical categories. Involvement of serum antibodies in infective larvae killing was assessed by antibody-dependent cellular adhesion and cytotoxicity assay. Cellular immune response was investigated by in vitro proliferation of peripheral blood mononuclear cells (PBMCs) and reactive oxygen species (ROS) generation in these cells after stimulation.</p>
</sec>
<sec>
<title>Results</title>
<p>Immune responses of EN and CP displayed almost similar level of IgG to Wol Tl IF-1 while other three proteins had higher serum IgG in EN individuals only. Specific IgA, IgG1, IgG3 and IgM to Bm-TPP were high in EN subjects, while BmAF-Myo additionally showed elevated IgG2. Enhanced IgA and IgG3 were detected in both EN and CP individuals in response to Wol Tl IF-1 antigen, but IgG1 and IgM were high only in EN individuals.
<italic>w</italic>
Bm-LigA and BmAF-Myo exhibited almost similar pattern of antibody responses. PBMC isolated from EN subjects exhibited higher proliferation and ROS generation when stimulated with all three proteins except for Wol Tl IF-1.</p>
</sec>
<sec>
<title>Conclusions</title>
<p>Overall, these findings display high immunogenicity of all four proteins in human subjects and revealed that the EN population was exposed to both
<italic>B. malayi</italic>
and
<italic>Wolbachia</italic>
proteins simultaneously. In addition, immune responses to Wol Tl IF-1 suggest possible role of this factor in
<italic>Wolbachia</italic>
-induced pathological responses while immune responses to other three proteins suggest that these can be explored further as vaccine candidates.</p>
</sec>
<sec>
<title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1186/s13071-016-1963-x) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
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