| First Author | Aoki R | Year | 2013 |
| Journal | J Invest Dermatol | Volume | 133 |
| Issue | 9 | Pages | 2170-9 |
| PubMed ID | 23528820 | Mgi Jnum | J:200049 |
| Mgi Id | MGI:5506862 | Doi | 10.1038/jid.2013.150 |
| Citation | Aoki R, et al. (2013) Mast Cells Play a Key Role in Host Defense against Herpes Simplex Virus Infection through TNF-alpha and IL-6 Production. J Invest Dermatol 133(9):2170-9 |
| abstractText | The essential contribution of mast cells (MCs) to bacterial host defense has been well established; however, little is known about their role in viral infections in vivo. Here, we found that intradermal injection with herpes simplex virus 2 (HSV-2) into MC-deficient Kit(W/Wv) mice led to increased clinical severity and mortality with elevated virus titers in HSV-infected skins. Ex vivo HSV-specific tetramer staining assay demonstrated that MC deficiency did not affect the frequency of HSV-specific cytotoxic T lymphocytes (CTLs) in draining lymph nodes. Moreover, the high mortality in Kit(W/W-v) mice was completely reversed by intradermal reconstitution with bone marrow-derived MCs (BMMCs) from wild-type, but not TNF(-/-) or IL-6(-/-) mice, indicating that MCs or, more specifically, MC-derived tumor necrosis factor (TNF) and IL-6 can protect mice from HSV-induced mortality. However, HSV did not directly induce TNF-alpha or IL-6 production by BMMCs; supernatants from HSV-infected keratinocytes induced the production of these cytokines by BMMCs without degranulation. Furthermore, IL-33 expression was induced in HSV-infected keratinocytes, and blocking the IL-33 receptor T1/ST2 on BMMCs significantly reduced TNF-alpha and IL-6 production by BMMCs. These results indicate the involvement of MCs in host defense at HSV-infected sites through TNF-alpha and IL-6 production, which is induced by keratinocyte-derived IL-33. |
