IL-17A-producing resident memory γδ T cells orchestrate the innate immune response to secondary oral Listeria monocytogenes infection

Memory gamma delta T cells are important for the clearance of Listeria monocytogenes infection in the intestinal mucosa. However, the mechanisms by which memory gamma delta T cells provide protection against secondary oral infection are poorly understood. Here we used a recombinant strain of L. monocytogenes that efficiently invades the intestinal epithelium to show that V gamma 4(+) memory gamma delta T cells represent a resident memory (Trm) population in the mesenteric lymph nodes (MLNs). The gamma delta Trm exhibited a remarkably static pattern of migration that radically changed following secondary oral L. monocytogenes infection. The gamma delta Trms produced IL-17A early after rechallenge and formed organized clusters with myeloid cells surrounding L. monocytogenes replication foci only after a secondary oral infection. Antibody blocking studies showed that in addition to IL-17A, the chemokine receptor C-X-C chemokine receptor 3 (CXCR3) is also important to enable the local redistribution of gamma delta Trm cells and myeloid cells specifically near the sites of L. monocytogenes replication within the MLN to restrict bacterial growth and spread. Our findings support a role for gamma delta Trms in orchestrating protective immune responses against intestinal pathogens.