Long-lived TRM cells derive from effector TH17 cells and are essential for an immediate response against antibiotic resistant bacterial infection.

MC AMEZCUA VESELY; GAGLIANI, NICOLA; BIELECKI, PIOTR; FLAVELL, RICHARD A

Rehovot

Congreso; Cell Conference; 2018

Weisman Institute

Mucosal barrier surfaces serve as the critical first line of defenseseparating our bodies from the plethora of pathogenicmicroorganism that inhabit our environment. Although emergingevidence has revealed a population of tissue resident memory Tcells (TRM) reside at these sites (1, 2), their origins and directcontribution to host defense remains elusive. Here we show for thefirst time that these TRM cells derive from effector- Th17 cells andthey serve as the essential mediators of microbial clearance duringthe memory immune response. Using a polyclonal fate mousemodel (3) of bacterial immunization-infection(4), in combinationwith parabiosis and depletion studies, we demonstrate that in-situmemory Th17 cells play an essential role in respiratory defenseand bacterial clearance. They are organized into a spatial nichesurrounding the airways, maintained by LEC derived IL7, andrapidly generate Il17a and IFNγ after infection to trigger neutrophilinfiltration and bacterial elimination. Our findings reveal the preciseorigin, spatial organization, longevity and function of bacterialspecificTRM exTh17 cells, with important implications for targetedvaccination design strategies and host immunity.