Javed N Agrewala
Indian Institute of Technology Ropar,India
Title: Host directed therapy through Clec4e: an innovative strategy to control the intracellular survival of Mycobacterium tuberculosis
Biography
Biography: Javed N Agrewala
Abstract
Host-directed therapies are gaining considerable impetus following the observation that there is an enhancement in the emergence of drug-resistant strains of pathogens due to antibiotics therapy. Therefore, there is an urgent need to exploit alternative and novel strategies directed to host molecules to successfully restrict the infections. The C-type lectin receptor (Clec4e) and Toll-like receptor (TLR-4) expressed by the host cells are the first line defense system to encounter pathogens. Therefore, for the first time, we exploited the role of signaling of macrophages through Clec4e in association with TLR-4 (C4.T4) in restricting the proliferation Mtb. Intriguingly, we observed significant improvement in the host immunity and decline in the bacterial load in the lungs of Mtb-infected mice and Guinea pigs. Further, intracellular killing of Mtb was achieved with 10-fold lesser dose of isoniazid or rifampicin in conjunction with C4.T4 than the drugs alone. Activation of NF-κB, phosphorylation of PI3K, STAT-1 and lysosome biogenesis, resulted in repressed Il-10 and Il-4 genes expression and enhanced autophagy. For the first time, the present finding unveils the novel role of Clec4e in inducing autophagy. This study suggests a novel immunotherapy involving Clec4e in conjunction with TLR-4 in restricting the survival of Mtb through autophagy.