The innate immune system relies on germ-line encoded receptors to induce anti-microbial responses. There are several classes of these receptors collectively termed as pathogen recognition receptors (PRRs). Toll-like receptors (TLRs) are a family of PRRs that detect invading pathogens and play an essential role in the induction of innate immune responses. Targets of TLR-mediated recognition are conserved products of microbial metabolism that are invariant among a large group of pathogens. Recognition of microbial ligands by TLRs leads to induction of anti-microbial and pro-inflammatory genes that are important for immediate protection of the host. TLRs also control initiation of adaptive immune responses by inducing maturation of dendritic cells (DCs). Maturation of DCs is a complex process and is an essential first step in a series of events leading to priming of naive T cells. My lab focuses on understanding the mechanisms by which DCs and DC derived cytokines influence naive T cell activation. We are specifically interested in identification and characterization of innate signals responsible for generation and maintenance of CD4 and CD8 memory T cells. A related area of work focuses on understanding how different cell types in the body influence induction of adaptive immune responses. We use genetically engineered mouse models that have restricted TLR expression in specific cell types (DCs, Macrophages and B cells) to address questions of contributions of these cells to innate and adaptive immunity.
A second area of research in the lab involves elucidating the role of TLRs in B cell activation. B lymphocytes are unique in the sense that they express functional receptors of both innate and adaptive immune system. Although TLR ligands have been traditionally used as B cell mitogens, T-dependent antibody responses are significantly enhanced when both B cell receptor (BCR) and TLRs are engaged at the same time. This suggests that direct sensing of pathogens by B cells is necessary for optimal activation of B cells for full blown antibody responses. We are interested in understanding the molecular mechanisms by which TLRs expressed on B cells can influence the initiation and maturation of B cell responses.
Our work has important implications for understanding protective responses to infections, altered responses causing auto-immunity and for developing efficacious vaccines.
RESEARCH INTERESTS
Immunology
Innate Immunity
TLRs and adaptive immunity
Dendritic cell biology
SIGNIFICANT PUBLICATIONS
Chandrashekhar Pasare and Ruslan Medzhitov, "Control of B cell responses by Toll-like receptors" Nature, 438(7066):364-368, November 2005
Chandrashekhar Pasare and Ruslan Medzhitov, "Toll-dependent control mechanisms of CD4 T cell activation" Immunity, 21(5):733-741, November 2004
Chandrashekhar Pasare and Ruslan Medzhitov, "Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells." Science, 299(5609):1033-1036, February 2003
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