A role for syndecan-1 and claudin-2 in microbial translocation during HIV-1 infection

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)306-315
Number of pages10
JournalJournal of Acquired Immune Deficiency Syndromes
Volume55
Issue number3
DOIs
StatePublished - Nov 1 2010

Keywords

  • HIV-1
  • claudin-2
  • immune activation
  • intestinal epithelium
  • microbial translocation
  • syndecan-1

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