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

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

Farmington, CT

Simposio; ImmunoGenomics Symposium; 2014

The Jackson Laboratory for Genomic Medicine

Intestinal mucosa shapes the immune system by interacting with commensal bacteria while maintaining bacterial pathogens at bay. In a 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 tested the 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 the IL-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. In addition, neutrophils depletion and forced gamma delta TCR downregulation abrogated cluster formation. Interestingly, we detected IL-17RA+ monocytes in the mLN that increased after rechallenge that can mediate the cell recruitement into clusters. Furthermore, we observed the induction of CXCL9 in areas sorrounding the clusters, which have been shown to mediate rapid mobilization of memory alpha beta T cells to prevent further spread of bacterial infection. 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 them LN 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.