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J Clin Invest. 2019 Feb 4. pii: 122530. doi: 10.1172/JCI122530. [Epub ahead of print]

Immune synapses between mast cells and γδ T cells limit viral infection.

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Program in Emerging Infectious Diseases, Duke-National University of Singapore (Duke-NUS) Medical School, Singapore.
Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA.
Department of Microbiology and Immunology, Young Loo Lin School of Medicine, National University of Singapore, Singapore.


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.


Antigen presenting cells; Immunology; Infectious disease; Mast cells; T cells

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