Auerbuch Stone Laboratory: Innate Immune Responses to the Human Pathogen Yersinia pseudotuberculosis
Recognition of bacterial pathogens by the innate immune system is of utmost importance to human health. However, successful bacterial pathogens have evolved mechanisms to manipulate innate immune defenses. We use the human gut pathogen and model organism Yersinia pseudotuberculosis to probe how the mammalian innate immune system specifically recognizes harmful, pathogenic bacteria as well as how bacterial pathogens cause disease in the face of the ensuing inflammatory response.
We are specifically interested in how mammalian innate immune cells respond to the Yersinia type III secretion system (T3SS), which is a specialized apparatus that injects bacterial effector proteins inside target host cells. These effector proteins alter normal host processes and facilitate bacteria growth. However, we and others have recently found that macrophages can distinguish between T3SS+ and T3SS- Yersinia, leading to a specific and robust immune response. Because only mammalian pathogens, not beneficial commensal bacteria, express T3SSs, this suggests that recognition of the T3SS enables mammalian cells to distinguish between harmful and harmless/beneficial bacteria.
Currently, we are:
- Investigating how mammalian cells recognize T3SS+ Yersinia.
- Identifying previously unknown factors that control the Yersinia T3SS and virulence.
- Using a novel approach to search for small molecule inhibitors of the Yersinia T3SS, for development of novel biochemical tools as well as therapeutics.