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.
Smith
Anthony J
AJ
Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455, USA.
Schacker
Timothy W
TW
Reilly
Cavan S
CS
Haase
Ashley T
AT
D000328:Adult; D001424:Bacterial Infections / Q000382:microbiology*; D018988:Bacterial Translocation; D018791:CD4 Lymphocyte Count; D057167:Claudins; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000276:immunology*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D053668:Syndecan-1 / Q000378:metabolism*
C491875:CLDN2 protein, human; D057167:Claudins; D008565:Membrane Proteins; D053668:Syndecan-1