Resident memory gamma delta T cells orchestrate response to secondary oral Lm infection

ROMAGNOLI PA; SHERIDAN BS; PHAM QM; KHANNA KM; LEFRANCOIS L

Pittsburgh, PA

Congreso; AAI IMMUNOLOGY 2014; 2014

The American Association of Immunologists, Inc.

Intestinal mucosa shapes the immune system by interacting with commensal bacteria while preventing the invasion of bacterial pathogens. In a physiological model of oral Listeria monocytogenes (Lm) infection, we have previously reported the generation of Lm-elicited protective memory V gamma4 V gamma delta T cells that reside in lamina propria and mesenteric lymph nodes (mln). Here we tested the hypothesis that Lm-elicited gamma delta T cells drive the accelerated secondary immune response to oral Lm infection in the mln. We show that memory gamma delta T cells secreted IL-17A and IFNγ in vivo and formed clusters with neutrophils that surrounded Lm aggregates in the mln 1 day after secondary oral Lm infection (d.p.r.). Neutralizing IL-17A disrupted cluster formation and neutrophil recruitment leading to delayed bacterial clearance. Cluster formation was also abrogated by forced gamma delta TCR downregulation.Together, these observations demonstrate that IL-17A, secreted by Lm-elicited memory gamma delta T cells, was essential for both recruitment of neutrophils to the mln, and for cluster formation to contain Lm during a secondary oral infection. In addition,we observed the induction of CXCL9 in areas surrounding the clusters, which has been shown to mediate rapid mobilization of memory gamma delta T cells to prevent further spread of bacterial infection. We believe these observations support an exciting new role for memory gamma delta T cells in the containment of intestinal pathogens.