HIV-1 efficient entry in inner foreskin is mediated by elevated CCL5/RANTES that recruits T cells and fuels conjugate formation with Langerhans cells

Male circumcision reduces acquisition of hiv-1 by 60%. hence,the foreskin is an hiv-1 entry portal during sexual transmission. we recently reported that efficient hiv-1 transmission occurs following 1 h of polarized exposure of the inner,but not outer,foreskin to hiv-1-infected cells,but not to cell-free virus. at this early time point,langerhans cells (lcs) and t-cells within the inner foreskin epidermis are the first cells targeted by the virus. to gain in-depth insight into the molecular mechanisms governing inner foreskin hiv-1 entry,foreskin explants were inoculated with hiv-1-infeceted cells for 4 h. the chemokine/cytokine milieu secreted by the foreskin tissue,and resulting modifications in density and spatial distribution of t-cells and lcs,were then investigated. our studies show that in the inner foreskin,inoculation with hiv-1-infected cells induces increased ccl5/rantes (1.63-fold) and decreased ccl20/mip-3-alpha (0.62-fold) secretion. elevated ccl5/rantes mediates recruitment of t-cells from the dermis into the epidermis,which is blocked by a neutralizing ccl5/rantes ab. in parallel,hiv-1-infected cells mediate a bi-phasic modification in the spatial distribution of epidermal lcs: attraction to the apical surface at 1 h,followed by migration back towards the basement membrane later on at 4 h,in correlation with reduced ccl20/mip-3-alpha at this time point. t-cell recruitment fuels the continuous formation of lc-t-cell conjugates,permitting the transfer of hiv-1 captured by lcs. together,these results reveal that hiv-1 induces a dynamic process of immune cells relocation in the inner foreskin that is associated with specific chemokines secretion,which favors efficient hiv-1 entry at this site. © 2011 zhou et al.