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

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

Cold Spring Harbor, NY

Conferencia; FUNDAMENTAL IMMUNOLOGY & ITS THERAPEUTIC POTENTIAL; 2015

Cold Spring Harbor Laboratories

Resident T cell memory provides efficient and rapid protection to mucosal tissues by sensing infection in situ and recruiting both innate and adaptive arms of the immune system. Using a relevant model of oral infection with Listeria monocytogenes (Lm), we tested the hypothesis that memory V gamma4 gamma delta T cells (Lm-elicited) are resident and participate in driving the accelerated immune response to secondary infection in the mln. We found thatLm-elicited gamma delta T cells reside in the mLN and are the main producers of IL-17A 1 day after secondary oral Lm infection(d.p.r.), which we found critical to control burden and induce clearance of bacteria. Most strikingly, we observed that Lm-elicited gamma delta T cells formed clusters with neutrophils surrounding Lm aggregates in the mln at 1 d.p.r.which were not detected in primary responses and were disrupted when IL-17A was blocked, neutrophils were depleted or TCR gamma delta downregulated. Moreover,CXCL1 and CXCL9 were detected in areas close to clusters. Together, these observations demonstrate that during a secondary oral Lm infection IL-17A secreted by Lm-elicited resident memory gamma delta T cells is critical for the early recruitment of monocytes and neutrophils into the mLN to form large organized clusters that contain Lm and may also attract memory gamma delta T cells. 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.