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

Authors
 Ji Eun Oh  ;  Byoung-Chan Kim  ;  Dong-Ho Chang  ;  Meehyang Kwon  ;  Sun Young Lee  ;  Dukjin Kang  ;  Jin Young Kim  ;  Inhwa Hwang  ;  Je-Wook Yu  ;  Susumu Nakae  ;  Heung Kyu Lee 
Citation
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.113(6) : 762-771, 2016 
Journal Title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN
 0027-8424 
Issue Date
2016
MeSH
Animals ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Antiviral Agents/immunology* ; Colony Count, Microbial ; Dysbiosis/complications* ; Eosinophils/drug effects ; Eosinophils/metabolism ; Female ; Herpes Genitalis/immunology ; Herpes Genitalis/pathology ; Herpes Genitalis/virology ; Herpesvirus 2, Human/drug effects ; Immunity, Innate*/drug effects ; Interferon-gamma/biosynthesis ; Interleukin-33/metabolism* ; Mice, Inbred C57BL ; Microbiota/drug effects ; Mucous Membrane/immunology ; Mucous Membrane/pathology* ; Mucous Membrane/virology ; Peptide Hydrolases/metabolism ; T-Lymphocytes/drug effects ; Vagina/drug effects ; Vagina/immunology* ; Vagina/pathology ; Vagina/virology
Keywords
IL-33 ; commensal microbiota ; dysbiosis ; genital tract ; herpes simplex virus type 2
Abstract
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 IFN 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 IL-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 IFN-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.
Files in This Item:
T201600496.pdf Download
DOI
10.1073/pnas.1518589113
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Yu, Je Wook(유제욱) ORCID logo https://orcid.org/0000-0001-5943-4071
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/146429
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