Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 129, Issue 3, Pages 1094-1108Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI122530
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Funding
- National Medical Research Council (NMRC) of Singapore [NMRC/CBRG/0084/2015]
- Duke-NUS Medical School
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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.
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