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; 2013

Marine Biology Laboratories

The intestinal mucosa influence the immune system by interacting with commensal bacteria while preventing invasion of bacterial pathogens. In a relevant model of oralListeria monocytogenes (Lm) infection, we have previously reported the generation of protective memory Vgamma4 Vdelta1 T cells (Lm-elicited) that reside within the lamina propria and mesenteric lymph nodes (mln) of Lm immune micea nd do not appear to recirculate. In this study, we tested the hypothesis that memory Lm-elicited gamma delta T cells participate in driving the accelerated immune response to a secondary infection in the mln. Here, we show that Lm-elicited gamma delta T cells secreted IL-17A and IFNγ in the mln in vivo 1 day after secondary oralLm infection (d.p.r.). We also observed that Lm-elicited gamma delta T cells formed clusters with neutrophils that surrounded Lm aggregates in the mLN 1 d.p.r. but not following a primary response. Neutralizing IL-17A disrupted cluster formation and neutrophil recruitment leading to elevated bacterial burden. On the other hand, formation of clusters was affected by forced gamma delta TCR downregulation. Together, these observations demonstrate that IL-17A, secreted by Lm-elicited gamma delta T cells, was crucial to recruit neutrophils into forming clusters that can contain Lm during a secondary oral infection. We believe these findings support an exciting new role for memory gamma delta T cells in the containment of intestinal pathogens.