The skin is an important barrier to infections and contains resident immune cells poised to respond to pathogens. Tissue-resident mast cells are critical for pathogen surveillance and initial response. In this episode, Ashley St. John discusses her work, which reveals a previously unrecognized interaction between mast cells and γδ T cells in the skin that is critical for clearance of dengue virus (DENV). The results of this study indicate that mast cells serve as nonconventional antigen-presenting cells that are poised to activate γδ T cells early during viral infection and limit disease.
Mast cells (MCs) are immune sentinels, but whether they also function as antigen-presenting cells (APCs) remains elusive. Using mouse models of MC deficiency, we report on MC-dependent recruitment and activation of multiple T cell subsets to the skin and draining lymph nodes (DLNs) during dengue virus (DENV) infection. Newly recruited and locally proliferating γδ T cells were the first T cell subset to respond to MC-driven inflammation, and their production of IFN-γ was MC dependent. MC–γδ T cell conjugates were observed consistently in infected peripheral tissues, suggesting a new role for MCs as nonconventional APCs for γδ T cells. MC-dependent γδ T cell activation and proliferation during DENV infection required T cell receptor (TCR) signaling and the nonconventional antigen presentation molecule endothelial cell protein C receptor (EPCR) on MCs. γδ T cells, not previously implicated in DENV host defense, killed infected targeted DCs and contributed to the clearance of DENV in vivo. We believe immune synapse formation between MCs and γδ T cells is a novel mechanism to induce specific and protective immunity at sites of viral infection.
Chinmay Kumar Mantri, Ashley L. St. John