The goal of my laboratory is to understand the cellular and molecular mechanisms that account for host resistance to protozoan parasites. We seek to decipher how innate immune cells cooperate in the regulation of IFN-gamma responses to the infection.
Expertise within my laboratory includes: innate immune cell biology, Toll-like receptors, mouse models of innate immune deficiencies, and the regulation of inflammatory responses by the innate immune system.
Our approach has been multidisciplinary, ranging from the creation of new mouse models with altered innate immune functions, to detailed biochemical and structural analyses of TLRs involved in recognition of protozoan parasites. The innovative use of cell type-specific ablation of the TLR/IL-1R adaptor protein MyD88 using the Cre-lox system has allowed us to dissect the mechanism by which innate immune cell collaborate to kill Toxoplasma organisms and to restrict their expansion, which is necessary to achieve protection from infection (PNAS, 2011; Nature Immunology, 2013). In a paper published in The Journal of Biological Chemistry in 2011 we established that TLR11, a protozoan protein sensor, has an intracellular localization that is controlled by a chaperone protein, Unc93B1. More recently (PNAS, 2013; Infection & Immunity, 2014; JI, 2015), we revealed that IFN-gamma can be produced by neutrophils. This is a major finding since neutrophils are the most numerous immune cell type. Our results revealed a new arm in innate immunity that addresses many basic and medically important questions in the field.
Our recent studies comparing T. gondii infected gnotobiotic (germ-free) animals to conventional mice have established that the immunostimulatory signals induced by commensal bacteria have major effects on the outcomes of the parasitic infections (Cell Host & Microbe, 2009, Nature Immunology, 2013). We are particular interested in understanding how the intestinal microbiota regulates host defense, tissue immunity and inflammation.