The primary goal of my translational research is to improve the understanding of environmental effects on human health and human immunity during infections such as with Mycobacterium tuberculosis (M.tb), the bacterium that causes TB. For the past 15 years my lab, in collaboration with others, has spearheaded research on human lung immune responses to M.tb. Our findings helped to establish the concept of compartmentalization of immune responses to the lungs in human pulmonary TB. Recent studies from my lab with co-investigators at EOHSI and at the University of Southern California (USC), have shown that stimulation of peripheral blood mononuclear cells (PBMC) with diesel exhaust particles (DEPs) alter cytokine production and toll-like receptor-mediated M.tb-specific cell activation pathways. DEPs are major components of aerosolized urban ambient fine particulate matter (PM). We noted that the production of critical M.tb-induced pro-inflammatory cytokines such as IFN-gamma, TNF-alpha, IL-1 beta, and IL-6 was reduced in a DEP dose-dependent manner in PBMC. Furthermore, inhibition of expression of many NF-kB and IFN regulatory signaling pathway target genes was observed upon DEP stimulation in non-infected cells. These data suggest that DEPs downregulate M.tb-induced cytokine and gene expression responses thus significantly compromising antimycobacterial host immune responses.

Human antimycobacterial immunity; Human lung immunology during mycobacteriumtuberculosis infection and disease; Effects of particulate matter on antimycobacterial immunity