Evaluation of immune response elicited By recombinant brugia malayi asparaginyl T rna synthetase rbmasnrs in lymphatic Filariasis

Abstract

A hallmark of lymphatic filariasis (LF) is the development of antigenspecific immunosuppression and long-term pathology with disability leading to elephantiasis. The role of parasite antigens modulating the immune environment of the host is an integral part of pathology of these sequelae but all the mechanisms that lead to these outcomes are still unclear. The current study attempts to dissect the immune responses of aminoacyl-tRNA synthetases (AARS) with emphasis on Brugia malayi Asparaginyl-tRNA synthetase (BmAsnRS) as it is one among the highly expressed excretory/secretory protein and is present in different stages of the life cycle of the parasite. This warrants investigation to elucidate the immune effects of BmAsnRS on the host and its role in filarial pathology as it has not been studied earlier. Hence, in this study, the immunological effects of rBmAsnRS were studied in semi-permissive filarial animal model Balb/c mice and on clinically defined human samples for LF. In mice study, humoral responses showed considerable titer levels with IgG2a isotype followed by IgG2b and IgG1. Immunoreactivity studies with clinical samples showed significant humoral responses especially in Endemic Normal (EN) with marked levels of IgG1 and IgG2 followed by IgG3. The cell-mediated immune response evaluated by splenocytes and Peripheral Blood Mononuclear cells (PBMC) proliferation, did not yield significant difference when compared to control groups. Cytokine profiling and qRTPCR analysis of mice samples immunized with rBmAsnRS showed elevated levels of IFN- , IL-10, Cytotoxic T Lymphocyte Associated Protein newline