Our research group is interested in investigating the various immune evasion strategies adopted by the filarial nematode Brugia malayi to overcome the protective host immune response. The focal points of research are several excretory-secretory (ES) products of the filarial nematode and their effect on host immune cells. We are specifically interested in elucidating the molecular mechanism behind functional impairment of different subsets of host dendritic cells and macrophages during the early stages of host-parasite interaction. Finding out the reasons behind alternative activation of host macrophages and impaired priming of the host adaptive immune response is an important aspect of our research work. In addition to this, we are also interested in elucidating the role of eosinophils during Tropical Pulmonay Eosinophilia (TPE) which is a rare, but fatal manifestation of filariasis. The lab also routinely carries out screening of synthetic and natural products for evaluation of their anti-filarial activity both in vitro and in vivo using rodent models of filarial infection.
Lymphatic filariasis (LF)- An introduction
LF is an incapacitating neglected tropical disease that is caused by filarial nematodes Wuchereria bancrofti,
Brugia malayi and Brugia timori. Several species of mosquitoes are vectors of this disease which currently affects about 1.2
billion people in more than 80 countries. Approximately 65% of these live in the south-east asia region including India where
people in 17 states and 6 union territories are at risk of infection. LF’s most recognizable symptoms are elephantiasis,
hydrocele and enlargement of breasts which causes disability, disfigurement, and even impairment of the body’s ability to fight
infection. Currently available mainstay drugs viz. Diethylcarbamazine (DEC), Ivermectin (IVM) and Albendazole (ALB) are mainly
microfilaricidal in nature and have only modest adulticidal activity which means that they are effective in stopping transmission
of the disease, but do not kill the adult worm. Though newer strategies based on targeting the Wolbachia endosymbiont which is
essential for worm fertility and survival are being studied, vaccine for any filarial parasite is not yet a reality.
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.
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.
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