Immune synapses between mast cells and [gamma][delta] T cells limit viral infection

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 [gamma][delta] T cells were the first T cell subset to respond to MC-driven inflammation, and their production of IFN-[gamma] was MC dependent. MC-[gamma][delta] T cell conjugates were observed consistently in infected peripheral tissues, suggesting a new role for MCs as nonconventional APCs for [gamma][delta] T cells. MC-dependent [gamma][delta] 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. [gamma][delta] 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 [gamma][delta] T cells is a novel mechanism to induce specific and protective immunity at sites of viral infection.
Introduction Mast cells (MCs) are tissue-resident cells that are distributed throughout the dermis, where they have an evolutionarily conserved responsibility to the host for pathogen surveillance (1). Although MCs have [...]