Dysbiosis-induced IL-33 contributes to impaired antiviral immunity in the genital mucosa

Commensal microbiota are well known to play an important role in antiviral immunity by providing immune inductive signals; however, the consequence of dysbiosis on antiviral immunity remains unclear. We demonstrate that dysbiosis caused by oral antibiotic treatment directly impairs antiviral immunity following viral infection of the vaginal mucosa. Antibiotic-treated mice succumbed to mucosal herpes simplex virus type 2 infection more rapidly than water-fed mice, and also showed delayed viral clearance at the site of infection. However, innate immune responses including type I interferon and proinflammatory cytokine production at infection sites, as well as induction of virus-specific CD4 and CD8 T cell responses in draining lymph nodes, were not impaired in antibiotic-treated mice. By screening the factors controlling antiviral immunity, we found that interleukin-33, an alarmin released in response to tissue damage, was secreted from vaginal epithelium after the depletion of commensal microbiota. This cytokine suppresses local antiviral immunity by blocking the migration of effector T cells to the vaginal tissue, thereby inhibiting the production of interferon-γ, a critical cytokine for antiviral defense, at local infection sites. These findings provide insight into the mechanisms of homeostasis maintained by commensal bacteria, and reveal a deleterious consequence of dysbiosis in antiviral immune defense.
Publisher
Awaji Forum Organizing Committee
Issue Date
2016-09-08
Language
ENG
Citation

The 15th Awaji International Forum on Infection and Immunity

URI
http://hdl.handle.net/10203/213404
Appears in Collection
MSE-Conference Papers(학술회의논문)
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