Role of host immune cells during filariasis:
Parasites have evolved many diverse and novel strategies to evade the host immune response which includes dampening of the host’s pro-inflammatory cytokine response, attenuating the functions of innate immune cells, generating regulatory T cells and impairing the activation, maturation and functions of host macrophages and dendritic cells (DCs). Though few reports have looked into the role of primary host DCs during the very early stages of filarial infection, DC subset specific studies are not only lacking but it is also not clear as to what extent these subsets are affected during the early stages of filarial infection. One of the main focus in the lab is therefore to identify different DC subsets in the host lymphoid organs and study their functional impairment in terms of impaired antigen uptake and presentation capacity that leads to selective attenuation of their T cell proliferation capacity and finding out ways as to how boosting of initial host immune response will be better suited to tackle the immunosuppression caused by the filarial nematode. In addition to this, finding out the reasons behind alternative activation of host macrophages and subsequent impaired priming of the host adaptive immune response is an important aspect of our research work.
Role of eosinophils during Tropical Pulmonary Eosinophilia (TPE):
TPE is a rare and serious inflammatory disorder of the lungs that is seen in a small minority of patients infected with filarial parasites Wuchereria bancrofti and Brugia malayi. Untreated TPE can lead to lung fibrosis and even death of patients. Lung lavage and lung biopsies of TPE patients show dominance of eosinophils that are correlated with pathological manifestations of TPE. However, eosinophils are very fragile cells, their low numbers and dual nature (protective and pathological) makes their isolation extremely difficult. Interestingly, it is this behavior of eosinophils that has made the immunological etiology of TPE very confusing and complicated. Our lab has recently developed a mouse model of TPE that exhibits cardinal features of human TPE pathogenesis. Using Flow cytometry, we successfully identified and sorted eosinophils to high purity. Efforts are on to identify genes and proteins of eosinophils that are differentially expressed under TPE conditions as they might play a central role in the pathogenesis of TPE.
Immunogenicity and protective efficacy of Filarial/Wolbachial antigens: Wolbachia, an endosymbiotic intracellular bacterium of the filarial nematode helps in their growth and development, regulates fecundity in female worms and contributes to the immunopathogenesis of the disease. However, genes and proteins of Wolbachia that may act as putative vaccine candidates are not known. Our research group is interested in investigating the immunogenecity of various Brugia malayi proteins and Wolbachial antigens that modulate the protective host immune response. The focal points of research are several excretory-secretory (ES) products of the filarial nematode and its endosymbiont.
Drug target and Drug Discovery: The lab routinely carries out screening of synthetic and natural products for evaluation of their anti-filarial activity using both in vitro and in vivo approaches. Adult worm and microfilariae motility assay, MTT assay as well as primary (Meriones unguiculatus) and secondary rodent model of filarial infection (Mastomys coucha) are routinely employed to identify the most promising natural product or synthetic compound.