Progressive Proximal-to-Distal Reduction in Expression of the Tight Junction Complex in Colonic Epithelium of Virally-Suppressed HIV+ Individuals

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While antiretroviral therapy for HIV-infected patients is remarkably effective in suppressing viral replication and preventing progression to AIDS, treated patients still have a shorter life expectancy due to increased risks for non-AIDS associated morbidities. Recent data showed that these complications are associated with chronic systemic inflammation, and it is hypothesized that bacterial products breaching the intestinal barrier may cause the inflammation. It is known that HIV induces persistent intestinal mucosal immunodeficiency, but evidence for structural damage to the intestinal epithelium is lacking in the antiretroviral-treated patient population. Here, we characterized the intestinal epithelial damage that leads to increased intestinal permeability in this population. We found that while the colonic epithelial layer is intact microscopically, intercellular tight junctions (TJ) are down-regulated at the transcriptional and translational levels. We observed further that TJ transcripts progressively decrease along the proximal-to-distal HIV gut. Concurrent alterations in the levels of non-TJ epithelial transcripts suggest that epithelial cells in the HIV gut are transcriptionally dysregulated. Our data provide evidence that TJ disruption is a novel mechanism for increasing colonic permeability in the antiretroviral-treated HIV patient, which may then result in systemic inflammation and associated complications.

Vyšlo v časopise: Progressive Proximal-to-Distal Reduction in Expression of the Tight Junction Complex in Colonic Epithelium of Virally-Suppressed HIV+ Individuals. PLoS Pathog 10(6): e32767. doi:10.1371/journal.ppat.1004198
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004198

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