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

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

Woods Hole, MA

Conferencia; New England Immunology Conference; 2014

Marine Biology Laboratories

Intestinal mucosa provides a niche to commensal bacteria while maintaining bacterial pathogens at bay. Ina relevant model of oral infection with Listeria monocytogenes (Lm), we previously reported the generation of protective memory Vgamma4 within the lamina propria and mesenteric lymph nodes (mLN) of Lm immune mice. In this study, we testedthe hypothesis that resident memory gamma delta T cells participate in driving the accelerated immune response to secondary infection in the mLN. Here, we show that Lm-elicited gamma delta T cells reside in the mLN and secrete the majority of theIL-17A produced in the mLN, critical to control bacterial burden and induce clearance 1 day after secondary oral Lm infection (dpr). We observed memory gamma delta T cells forming clusters with neutrophils surrounding Lm aggregates in the mLN 1 dpr and that these clusters were disrupted when IL-17A was blocked. Interestingly, we detected IL-17RA+ monocytes in the mLN that increased after rechallenge that can mediate the cell recruitement into clusters. Together,these observations demonstrate that during a secondary oral infection IL-17A secreted by Lm specific memory gamma delta T cells is critical for the early recruitment of neutrophils into the mLN to form large organized clusters to contain Lm. In addition, we suggest that IL17RA+ monocytes in the mLN serve as important mediators of the secondary immune response producing chemokines to further recruit monocytes, neutrophils and memory gamma delta T cells to finally clear Lm. We believe these findings support an exciting new role for memory gamma delta T cells in sensing infection to orchestrate a hierarchy of immune cells for the containment of intestinal pathogens.