The role of commensal microbiota on CD8 T cell response to Listeria monocytogenes infection

Abstract

Abstract Commensal microbiota is composed of trillions of microorganisms including fungi, protozoans, viruses and bacteria, which have co-evolved with the host immune system. In particular, the gut is the largest reservoir of microorganisms that are involved in dynamic interaction with the immune system, including maintaining intestinal homeostasis, induction of several metabolic pathways, and protection from pathogenic microbes. To better understand the mechanisms involved microbiota-mediated protection from the pathogenic bacteria, we have studied oral infection of germ-free (GF) mice with a strain of Listeria monocytogenes (L. monocytogenes) that has been engineered to efficiently infect the intestinal epithelial cells of the mouse. We found that GF mice are more susceptible to orally administrated L. monocytogenes than conventional SPF mice, with an increased Listeria burden in the mLN, small intestine and feces. In addition, in the infected GF mice, L. monocytogenes-specific CD8 T cells were vigorously activated and induced to differentiate into memory precursor effector cells (MPECs) and tissue resident memory (CD69+ CD103+) T cells in the intestinal epithelium at a faster rate than in infected SPF mice. L. monocytogenes-specific CD8 T cells in GF mice also secrete more effector cytokines, such as interferon-γ and tumor necrosis factor-α. The mechanisms by how commensal microbiota confers resistance to infection by L. moncoytogenes in SPF mice is currently under investigation.