Roles of mast cells on viral infection and mast cell-based immunotherapy

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Mast cells have long been considered as major effector cells in type I-allergic responses. Recent studies, however, have revealed the additional importance of mast cells in host defense against pathogens, especially bacteria. Although we have recently reported that cutaneous mast cells express functional Toll-like receptors (TLRs) that recognize viral components, it remains largely unknown whether mast cells are involved in host defense against viruses. We hypothesized that degranulation and inflammatory cytokine production by mast cells may be induced upon herpes simplex virus (HSV) infection, thus being involved in the inflammatory and immune responses against the virus. To test this, we used murine fetal skin-derived cultured mast cells (FSMC). Rapid (within 10 min) degranulation by FSMC was induced in a virus number-dependent fashion without affecting cell viability, when HSVwas added to FSMC cultures (β-hexosaminidase assay). The viral components were detected within 24 h after the infection (immunohistochemistry). In addition, inflammatory cytokines (i.e., TNFα, IL-6, and IFNβ) were not induced in the culture supernatants 24 h post infection. Upon inoculation of HSV (5 x 10^5 PFU) intradermally into BALB/c mice, the dermal infiltrates and significant increase in the number of degranulated mast cells were observed within 2 h (toluidine blue staining). These results indicate that cutaneous mast cells degranulate without elaborating inflammatory cytokines upon HSV infection, thus participating in the induction of inflammatory responses and the subsequent acquired immune responses against the virus.