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
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 129 Issue 3 Pg. 1094-1108 (03 01 2019) ISSN: 1558-8238 [Electronic] United States
• PMID: 30561384 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Video-Audio Media)

Chemical References

• Endothelial Protein C Receptor
• Receptors, Antigen, T-Cell, gamma-delta

Topics

• Animals
• Dendritic Cells (immunology, pathology)
• Dengue (genetics, immunology, pathology)
• Dengue Virus (immunology)
• Disease Models, Animal
• Endothelial Protein C Receptor (genetics, immunology)
• Immunological Synapses (genetics, immunology)
• Mast Cells (immunology, pathology)
• Mice
• Mice, Transgenic
• Receptors, Antigen, T-Cell, gamma-delta (genetics, immunology)
• Skin (immunology, pathology)
• T-Lymphocytes (immunology, pathology)