4.7 Article

Interferon-β induced in female genital epithelium by HIV-1 glycoprotein 120 via Toll-like-receptor 2 pathway acts to protect the mucosal barrier

期刊

CELLULAR & MOLECULAR IMMUNOLOGY
卷 16, 期 2, 页码 178-194

出版社

CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/cmi.2017.168

关键词

antiviral response; genital epithelium; HIV-1; IFN-beta; innate immunity; IRF-3; mucosal barrier; TLR2

资金

  1. Canadian Institutes of Health Research (CIHR) [FRN 126019]
  2. CIHR Team Grant on Mucosal Immunology of HIV Vaccine Development [FRN 138657]
  3. Ontario HIV Treatment Network (OHTN) Applied HIV Research Chair [AHRC 779]
  4. CIHR Banting Scholarship

向作者/读者索取更多资源

More than 40% of HIV infections occur via female reproductive tract (FRT) through heterosexual transmission. Epithelial cells that line the female genital mucosa are the first line of defense against HIV-1 and other sexually transmitted pathogens. These sentient cells recognize and respond to external stimuli by induction of a range of carefully balanced innate immune responses. Previously, we have shown that in response to HIV-1 gp120, the genital epithelial cells (GECs) from upper reproductive tract induce an inflammatory response that may facilitate HIV-1 translocation and infection. In this study, we report that the endometrial and endocervical GECs simultaneously induce biologically active interferon-beta (IFN beta) antiviral responses following exposure to HIV-1 that act to protect the epithelial tight junction barrier. The innate antiviral response was directly induced by HIV-1 envelope glycoprotein gp120 and addition of gp120 neutralizing antibody inhibited IFN beta production. Interferon-beta was induced by gp120 in upper GECs through Toll-like receptor 2 signaling and required presence of heparan sulfate on epithelial cell surface. The induction of IFN beta was dependent upon activation of transcription factor IRF3 (interferon regulatory factor 3). The IFN beta was biologically active, had a protective effect on epithelial tight junction barrier and was able to inhibit HIV-1 infection in TZM-bl indicator cells and HIV-1 replication in T cells. This is the first report that recognition of HIV-1 by upper GECs leads to induction of innate antiviral pathways. This could explain the overall low infectivity of HIV-1 in the FRT and could be exploited for HIV-1 prophylaxis.

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