Immune synapses between mast cells and γδ T cells limit viral infection
Chinmay Kumar Mantri, Ashley L. St. John
Chinmay Kumar Mantri, Ashley L. St. John
Published December 18, 2018
Citation Information: J Clin Invest. 2019;129(3):1094-1108. https://doi.org/10.1172/JCI122530.
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Research Article Immunology Infectious disease

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

Abstract

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.

Authors

Chinmay Kumar Mantri, Ashley L. St. John

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Figure 3

Defects in T cell recruitment to DENV-infected LNs in the MCPT5-Cre iDTR model of MC deficiency.

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Defects in T cell recruitment to DENV-infected LNs in the MCPT5-Cre iDTR...
(A) Schematic showing the timeline for DT and DENV injections. Mcpt5-Cre and Mcpt5-Cre/iDTR mice were injected with saline to serve as controls or with DT every week for 4 weeks for systemic MC depletion before infection. Mice were injected with saline or infected with 1 × 105 pfu DENV s.c. into the FP, and the popliteal LNs were collected 24 hours after infection. Single-cell suspensions of LN cells were stained to identify T cell subsets using the gating strategy in Supplemental Figure 1. T cell responses to DENV infection were compared among MC-sufficient Mcpt5-Cre/iDTR (saline-injected), MC-sufficient MCPT5-Cre (DT-injected), and MC-deficient Mcpt5-Cre/iDTR (DT-injected) mice. Number of (B) total T cells (CD3+), (C) NKT cells (CD3+NK1.1+), (D) γδ T cells (CD3+γδTCR+), (E) CD4+ T cells (CD3+CD4+), and (F) CD8+ T cells (CD3+CD8+) all showed MC-dependent recruitment to LNs during DENV infection in this c-Kit–independent model of MC deficiency. Data represent the mean ± SEM. *P < 0.05, ***P < 0.001, and ****P < 0.0001, by 2-way ANOVA with Sidak’s multiple comparisons test. n = 4–6 animals per group. The efficiency of MC depletion after injection with DT is shown in Supplemental Figure 4.