Communication between immune and stromal cells is key to immunological memory within pathogen infected tissues (360G-Wellcome-210703_Z_18_Z)

Pathogens trigger an accumulation of immune cells in the infected tissue. Incoming immune cells adapt to their new environment, communicating with infected stromal cells to ensure pathogen control. Tissues do not immediately return to homeostasis following pathogen clearance. Some pathogen-specific T cells remain, differentiating into Tissue Resident Memory cells (Trm). The tissues’ stromal cells also retain an imprint of the infection with prolonged expression of immune-related genes. Currently, we have only limited understanding of the cells and molecules involved in establishing and maintaining these infection-induced changes and how immune and stromal cell communication impacts on protective immunity. These are key question for vaccines that aim to induce immune protection within tissues to provide rapid protective immunity. This proposal is based on our findings that antigen-presentation and inflammatory cytokine production drives prolonged changes in lung CD4 Trm cells and epithelial cells and fibroblasts. Our key goals are to define the mechanistic basis for these changes by identifying the cells and molecules that influence the generation, maintenance and protective responses of infection-altered immune and lung stromal cells. This research will provide a conceptual breakthrough in our understanding of how cell commination influences protective memory and novel insights relevant to improved vaccine design.