Defining protective immunity within granulomas during enteric infection

Microbial pathogens claim the lives of millions of people worldwide each year, while millions more suffer from chronic infections.

Increases in antibiotic resistance threaten to undermine already limited treatment options, highlighting an urgent need for new therapeutic approaches.

Granulomas act as barriers to pathogen dissemination and form in response to a wide variety of infections, such as histoplasmosis, leishmaniasis and tuberculosis.

Although generally considered protective, these immune structures also provide a replicative niche from which pathogens can spread should the immune system be compromised. A major unanswered question has been how granulomas are sterilized and cleared. Solving this problem would enable us to alleviate granulomatous diseases.

Yet, the molecular basis of pathogen restriction within granulomas remains poorly understood.I recently identified granulomas as an unappreciated niche for enteropathogenic Yersinia invasion in the murine intestine.

My new preliminary data reveal that intestinal granulomas are sterilized by T lymphocytes, providing a novel tool to dissect the mechanistic basis of granuloma resolution.

With my experience in mucosal immunology and microbial pathogenesis, I aim to dissect how T cells orchestrate granuloma resolution to facilitate bacterial control.

Altogether, this proposal seeks to uncover fundamental mechanisms of pathogen restriction, with the long-term goal of developing new treatments for granulomatous diseases.