Journal
CELLULAR & MOLECULAR IMMUNOLOGY
Volume 16, Issue 2, Pages 178-194Publisher
CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/cmi.2017.168
Keywords
antiviral response; genital epithelium; HIV-1; IFN-beta; innate immunity; IRF-3; mucosal barrier; TLR2
Categories
Funding
- Canadian Institutes of Health Research (CIHR) [FRN 126019]
- CIHR Team Grant on Mucosal Immunology of HIV Vaccine Development [FRN 138657]
- Ontario HIV Treatment Network (OHTN) Applied HIV Research Chair [AHRC 779]
- CIHR Banting Scholarship
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available