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Wuchereria bancrofti filaria activates human dendritic cells and polarizes T helper 1 and regulatory T cells via toll-like receptor 4

Suprabhat Mukherjee 1, 2 Anupama Karnam 2 Mrinmoy Das 2 Santi Babu 1 Jagadeesh Bayry 2, *
* Corresponding author
2 CRC - Inserm U1138 - Immunopathologie et immunointervention thérapeutique
CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
Abstract : Interaction between innate immune cells and parasite plays a key role in the immunopathogenesis of lymphatic filariasis. Despite being professional antigen presenting cells critical for the pathogen recognition, processing and presenting the antigens for mounting T cell responses, the dendritic cell response and its role in initiating CD4+ T cell response to filaria, in particular Wuchereria bancrofti, the most prevalent microfilaria is still not clear. Herein, we demonstrate that a 70 kDa phosphorylcholine-binding W. bancrofti sheath antigen induces human dendritic cell maturation and secretion of several pro-inflammatory cytokines. Further, microfilarial sheath antigen-stimulated dendritic cells drive predominantly Th1 and regulatory T cell responses while Th17 and Th2 responses are marginal. Mechanistically, sheath antigen-induced dendritic cell maturation, and Th1 and regulatory T cell responses are mediated via toll-like receptor 4 signaling. Our data suggest that W. bancrofti sheath antigen exploits dendritic cells to mediate distinct CD4+ T cell responses and immunopathogenesis of lymphatic filariasis.
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Suprabhat Mukherjee, Anupama Karnam, Mrinmoy Das, Santi Babu, Jagadeesh Bayry. Wuchereria bancrofti filaria activates human dendritic cells and polarizes T helper 1 and regulatory T cells via toll-like receptor 4. Communications Biology, Nature Publishing Group, 2019, 2, pp.169. ⟨10.1038/s42003-019-0392-8⟩. ⟨inserm-02455413⟩

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