A Role for Syndecan-1 and Claudin-2 in Microbial Translocation During HIV-1 Infection

Microbial translocation from the gastrointestinal tract has been implicated in chronic activation of the immune system during progressive HIV-1 infection by ill-defined mechanisms. We recently identified a gene encoding syndecan-1 (SYN1) in microarray studies of HIV-1 infection in lymphatic tissues and show here that increased expression of SYN1 in the gut of HIV-1-infected individuals is associated with increased microbial translocation. We further show that: (1) microbial access to SYN1 in the intestinal epithelium could be mediated by compromised barrier function through the upregulation of claudin-2; (2) increases in SYN1 and microbial translocation are associated with systemic immune activation; and (3) SYN1 expression and microbial translocation are inversely correlated with peripheral blood CD4(+) T-cell counts. We thus propose a new mechanism in which claudin-2 and SYN1 work in concert to enhance microbial translocation across the intestinal epithelial barrier to contribute to chronic immune activation and CD4(+) T-cell depletion.