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Recombinant Wolbachia surface protein (WSP)-induced T cell responses in Wuchereria bancrofti infections

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Abstract

Human lymphatic filariasis is a debilitating parasitic disease characterized by downregulation of the host’s immune response in asymptomatic carriers along with profound hyperreactivity in chronic patients apart from putatively immune endemic normals. The endosymbiont Wolbachia, a bacterium of filarial nematodes has received much attention as possible chemotherapeutic target and its involvement in disease pathogenesis. The role of recombinant Wolbachia surface protein (rWSP), one of the most abundantly expressed proteins of the endosymbiont, in modulating cell-mediated immune responses in patients harboring Wuchereria bancrofti infections was evaluated in the current study. rWSP-induced lymphoproliferation with peripheral blood mononuclear cells suggested an impaired proliferative response in asymptomatic microfilaremic (MF) and symptomatic chronic pathology (CP) patients compared to endemic normals (EN). This was further supported by a significantly diminished expression of CD69 along with elevated levels of CD127 and CD62L in filarial patients (MF and CP) compared to EN. Further, rWSP induced the expression of regulatory T cell markers CTLA-4 and CD25 along with suppressor cytokines IL-10 and TGF-β in MF and CP patients compared to EN. However, the rWSP-stimulated expression of IFN-γ was diminished significantly in filarial patients compared to endemic normals. Thus, these findings suggest that WSP may also contribute to the suppression of immune responses seen in filarial patients.

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Abbreviations

BmA:

Brugia malayi adult crude extract

CD:

Cluster of differentiation

CFA:

Circulating filarial antigen

CP:

Chronic pathology

CTLA-4:

Cytotoxic T lymphocyte antigen

cDNA:

Complementary DNA

DEPC:

Diethyl pyrocarbonate

EN:

Endemic normal

FCS:

Fetal calf serum

FITC:

Fluorescein isothiocyanate

GPELF:

Global Programme for Elimination of Filariasis

ICT:

Immunochromatographic

IFN-γ:

Interferon gamma

IL:

Interleukin

LAL:

Limulus amoebocyte lysate assay

MDA:

Mass drug administration

MF:

Microfilaremics

mf:

Microfilariae

NEN:

Non-endemic normal

PBMC:

Peripheral blood mononuclear cells

PHA:

Phytohemagglutinin

PFA:

Paraformaldehyde

RNA:

Ribonucleic acid

RPMI:

Roswell Park Memorial Institute

RT-PCR:

Reverse-transcribed polymerase chain reaction

TReg :

T regulatory cells

WSP:

Wolbachia surface protein

W. bancrofti :

Wuchereria bancrofti

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Acknowledgments

The authors wish to thank Dr. Thomas B. Nutman, National Institute of Health (NIH), Bethesda, MD, USA for providing the reagents for the FACS analysis. We also thank the Department of Public Health and Preventive Medicine, Malaria and Filaria Division Government of Tamil Nadu, Chennai, India, for their help with the clinical samples. This work received funding from the Department of Science and Technology, New Delhi, India. CS was a recipient of the Senior Research Fellowship Award from CSIR, New Delhi, India. This work was supported in part by NIAID/DIR through the ICER program.

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Authors and Affiliations

  1. Centre for Biotechnology, Anna University, Chennai, 600025, India

    C. Shiny, N. S. A. Krushna, K. Haripriya & R. B. Narayanan

  2. NIH-TRC-ICER SAIC-Frederick, Inc., National Cancer Institute at Frederick, Chetpet, Chennai, 600003, India

    S. Babu

  3. Department of Public Health and Preventive Medicine, Government of Tamil Nadu, Chennai, 600006, India

    S. Elango

  4. Apollo Hospital, Greams Road, Chennai, 600006, India

    G. Manokaran

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  1. C. Shiny
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  2. N. S. A. Krushna
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  3. K. Haripriya
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  4. S. Babu
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  5. S. Elango
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  7. R. B. Narayanan
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Correspondence to R. B. Narayanan.

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Shiny, C., Krushna, N.S.A., Haripriya, K. et al. Recombinant Wolbachia surface protein (WSP)-induced T cell responses in Wuchereria bancrofti infections. Parasitol Res 110, 787–797 (2012). https://doi.org/10.1007/s00436-011-2553-7

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  • DOI: https://doi.org/10.1007/s00436-011-2553-7

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