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Parasitology Research

, Volume 110, Issue 2, pp 787–797 | Cite as

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

  • C. Shiny
  • N. S. A. Krushna
  • K. Haripriya
  • S. Babu
  • S. Elango
  • G. Manokaran
  • R. B. Narayanan
Original Paper

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.

Keywords

TReg Cell Lymphatic Filariasis Mass Drug Administration Filariasis Filarial Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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

Notes

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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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • C. Shiny
    • 1
  • N. S. A. Krushna
    • 1
  • K. Haripriya
    • 1
  • S. Babu
    • 2
  • S. Elango
    • 3
  • G. Manokaran
    • 4
  • R. B. Narayanan
    • 1
  1. 1.Centre for BiotechnologyAnna UniversityChennaiIndia
  2. 2.NIH-TRC-ICER SAIC-Frederick, Inc.National Cancer Institute at FrederickChennaiIndia
  3. 3.Department of Public Health and Preventive MedicineGovernment of Tamil NaduChennaiIndia
  4. 4.Apollo HospitalChennaiIndia

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