Resident memory γδ T cells orchestrate response to secondary oral Lm infection

Resident T cell memory provides protection to mucosal tissues by sensing infection and recruiting both innate and adaptive arms of the immune system. Using a model of oral infection with Listeria monocytogenes (Lm), we tested the hypothesis that memory Vγ4 γδ T cells (Lm-elicited) are resident and participate in driving the accelerated immune response to secondary infection in the mesenteric lymph node (mLN). We found that CXCR3+ Lm-elicited γδ T cells reside in the mLN and are the main producers of IL-17A, critical to control burden and induce clearance of bacterial, 1 day after secondary oral Lm infection. Most strikingly, we observed that Lm-elicited γδ T cells formed clusters with neutrophils surrounding Lm aggregates in the mLN that were disrupted by IL-17A blockade, neutrophil depletion, TCR γδ downregulation or CXCR3 blockade. Moreover, CXCL1 and CXCL9 were found in the cluster area. Together, these observations demonstrate that during secondary oral Lm infection IL-17A secreted by resident Lm-elicited γδ T cells is critical to recruit monocytes and neutrophils into clusters that contain Lm and may also attract memory αβ T cells. These findings support an exciting role for memory γδ T cells to orchestrate a hierarchy of immune upon infection to contain intestinal pathogens.