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High Tregs and systemic IL-10 expressions linked to the absence of sheath antibodies in lymphatic filariasis: implications on the persistence of residual infection

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Abstract

The persistence of residual infection is one of the major factors in failure of the Global Programme to Eliminate Lymphatic Filariasis (GPELF). The present study aims to explore the status of sheath antibody and regulatory T cells (Tregs) known to play key roles in clearance of parasite and patent filarial infection, in individuals with residual infection after MDA. A total of 61 microfilaremic (Mf) individuals were followed up after at least 6 rounds of MDA. Infection status of subjects was assessed through the detection of Mf and circulating filarial antigen (CFA). Antibodies to Mf sheath were determined by immuno-peroxidase assay (IPA). The expression of Tregs was measured by a flow cytometer. IL-10 and IFN-γ were evaluated using the commercially available ELISA kit. The sheath antibody was present in subjects who have cleared both Mf and CFA and absent in individuals who were found to be Mf /CFA positive. Further individuals carrying infection have significantly high levels of Tregs and IL-10. A positive correlation was observed between Tregs, IL-10, and CFA in infected individuals. In contrast, a negative correlation was observed between IFN-γ and IL-10 in both infected and uninfected subjects. Our study reveals that the absence of a sheath antibody and a high level of Tregs and IL-10 are the hallmarks of the persistence of residual filarial infection.

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All data pertaining to this study is published in the paper or included in the Supplemental Materials.

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Acknowledgments

We are grateful to all the participants of this study for their sincere cooperation throughout this study. We thankfully acknowledge the technical assistance rendered by Mr Minaketan Barik, Mr KC Parichha, and Mr Niranjan Sahu of the institute during the study. We express our gratitude to the village chiefs, field workers, and community members for their support during the study.

Funding

This work was supported by the Indian Council of Medical Research, New Delhi, India.

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Authors and Affiliations

  1. ICMR-Regional Medical Research Center, Chandrasekharpur, Bhubaneswar, Odisha, 751023, India

    Madhusmita Bal, Manoranjan Ranjit, Hemanta K. Khuntia, Ashok K. Satapathy, K. Gopinath Achary, Bhagirathi Dwibedi & Sanghamitra Pati

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  1. Madhusmita Bal
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Contributions

Conceptualization: Madhusmita Bal; methodology: Madhusmita Bal, Manoranjan Ranjit, and Bhagirathi Dwibedi; formal analysis and investigation: Madhusmita Bal, K. GopinathAchary, and Hemanta K. Khuntia; writing—original draft preparation: Madhusmita Bal; writing—review and editing: Manoranjan Ranjit and Madhusmita Bal; funding acquisition: Sanghamitra Pati; resources: Ashok K. Satapathy; supervision: Madhusmita Bal

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Correspondence to Madhusmita Bal.

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The Indian Council of Medical Research has granted the proposal and Human Ethical Committee of ICMR-Regional Medical Research Centre Bhubaneswar, Odisha, has approved the study.

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Supplementary Fig. 1

Lymphocytes were analyzed by flow cytometry after staining with anti-human CD4-FITC and anti-human CD25-PE. Figure shows the gating strategy of regulatory T Cells (CD4+ T cells expressing the highest level of CD25 i,e CD4+ CD25hi). % of Tregs frequencies were calculated from total lymphocyte gated (TIFF 757 kb)

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Bal, M., Ranjit, M., Khuntia, H.K. et al. High Tregs and systemic IL-10 expressions linked to the absence of sheath antibodies in lymphatic filariasis: implications on the persistence of residual infection. Immunol Res 69, 90–99 (2021). https://doi.org/10.1007/s12026-021-09175-7

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