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The goal of my research program is to investigate the cross-talk between innate and adaptive immunity against two intracellular pulmonary pathogens,聽 influenza and聽Mycobacterium tuberculosis聽(Mtb). Antigen presenting cells, such as macrophages or dendritic cells, fine-tune immune responses, by instructing an effective聽 level of activation, proliferation, and differentiation of na茂ve T cells. One聽 mechanism by which virulent pathogens successfully inactivate host defense mechanisms is by interrupting the cross-talk between innate and adaptive immunity.聽 APC initially sense pathogens through pathogen-associated molecular patterns (PAMPs) including Toll-like receptors (TLRs) and Nod-like receptors (NODs). This聽 initial recognition induces a cascade of inflammatory responses including cytokine/chemokine induction and recruitment of inflammatory cells to the site of infection. However, the pathogen-driven inflammatory response needs to be聽 tightly regulated by the host to prevent immune-pathology. Eicosanoids play an important聽 regulatory role in the host immune response including cell death programs that directly affect both innate and adaptive immunity. There are two major cell death pathways; apoptosis and necrosis. Several pathogens hijack cell death programs to their advantage. Recently we defined that eicosanoid-regulated cell death of聽Mtb-infected macrophages modulates both innate and T cell mediated immunity against聽Mtb.聽 Necrosis is a strategy that聽Mtb聽exploits to exit from macrophages and infect other cells. In contrast, apoptosis, characterized by an intact plasma membrane, is an innate defense聽 mechanism that reduces bacterial viability as well as enhancing T cell priming via cross-presentation of the antigen cargo of apoptotic macrophages by dendritic cells. Thus, we are interested in understanding the molecular mechanisms by which APC regulate the immune response to infectious diseases which may ultimately allow us to design better vaccines or targeted drugs against these two devastating diseases.聽

To achieve our research goals, we聽 have established mouse models of influenza pneumonia and聽M. tuberculosisas well as primary cell cultures. The laboratory has a dedicated 11-colour flow聽 cytometer LSR-II, an imaging technology, and the state-of-art BL2 facility,聽 which allows us to handle BL2 pathogens, including influenza virus for both聽in vitro聽and聽in vivo聽studies. The study with聽Mtb聽is being conducted through a collaboration with Dr. Marcel Behr in his laboratories containing a BL3 facility.