Abstract
Mucosal exposure to infected semen accounts for the majority of HIV-1 transmission events, with rectal intercourse being the route with the highest estimated risk of transmission. Yet, the impact of semen inflammation on colorectal HIV-1 transmission has never been addressed. Here we use cynomolgus macaques colorectal tissue explants to explore the effect of leukocytospermia, indicative of male genital tract inflammation, on SIVmac251 infection. We show that leukocytospermic seminal plasma (LSP) has significantly higher concentration of a number of pro-inflammatory molecules compared to normal seminal plasma (NSP). In virus-exposed explants, LSP enhance SIV infection more efficiently than NSP, being the increased viral replication linked to the level of inflammatory and immunomodulatory cytokines. Moreover, LSP induce leukocyte accumulation on the apical side of the colorectal lamina propria and the recruitment of a higher number of intraepithelial dendritic cells than with NSP. These results suggest that the outcome of mucosal HIV-1 infection is influenced by the inflammatory state of the semen donor, and provide further insights into mucosal SIV/HIV-1 pathogenesis.
Highlights
Mucosal exposure to infected semen accounts for the majority of HIV-1 transmission events, with rectal intercourse being the route with the highest estimated risk of transmission
Inflammatory cytokines, including IL-8, IL-6, IL-1ß, are enriched in seminal fluids from leukocytospermic individuals[26,27,28] and we reported an increase in inflammatory molecules in semen associated with leukocytospermia and SIV infection in nonhuman primates (NHPs)[29,30]
We previously reported that intestinal dendritic cells (DCs) migrate from the lamina propria inside the colonic epithelium following exposure to R5 HIV-1 through a CCR5-dependent mechanism to capture the virus and transfer the infection to receptive CD4+ T cells[8]
Summary
Mucosal exposure to infected semen accounts for the majority of HIV-1 transmission events, with rectal intercourse being the route with the highest estimated risk of transmission. These results suggest that the outcome of mucosal HIV-1 infection is influenced by the inflammatory state of the semen donor, and provide further insights into mucosal SIV/HIV-1 pathogenesis. The ability of seminal plasma, the acellular semen fraction, to enhance HIV1 transmission has been proven by its capacity to recruit HIV-1 target cells, including macrophages, DCs, and T cells, to the female reproductive tract (FRT)[12,17,18,19,20,21] and to increase infectivity, even at low viral titers[22]. There was significantly greater enhancement of SIV infection and DC recruitment in the presence of elevated cytokine concentrations when explants were exposed to leukocytospermic seminal plasma (LSP) compared to normal seminal plasma (NSP)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
