HIV infection is associated with significant mucosal inflammation

Abstract

BACKGROUND: HIV preferentially infects activated, memory CD4+ lymphocytes expressing requisite co-receptors. The gut mucosa is the body s largest immune organ, which in the healthy, normal condition is characterised by low-level inflammation and constitutive expression of chemokines and cytokines. The gut contains the body s largest number of activated, memory T cells, which express high levels of CCR5 and CXCR4 A. Inflammation with chemotactic chemokines recruiting additional activated immune cells, would potentially further increase infectible targets for HIV spread. METHODS: Colon biopsies from 6 HIV-infected individuals, 8 Inflammatory Bowel Disease (IBD) patients and 5 seronegative, healthy controls without organic bowel disease were compared. All but one HIV infected was on HAART. Plasma viral load was undetectable in three patients and differed between 4.4 5.7 logs in three patients. IBD patients included 5 with active disease, 3 in remission. Samples were immunohistochemically stained with monoclonal antibodies against CCR5, CXCR4, RANTES, MlP-l a and MIP-l f3 with expression evaluated at the single cell level by computerized in situ imaging. RESULTS: The expression of chemokine receptors CCR5 and CXCR4 was significantly increased in HIV-infected mucosal sections compared to both IBD in remission (IBDr) and seronegative controls (p<0.05). Sections from patients with active IBD showed a similar pattern of increased chemokine receptor expression. f3-chemokines including RANTES and MIPlf3, were significantly upregulated in HIV compared to IBDr and healthy controls (p<0.05). In active IBD there was increased expression of RANTES, compared to IBDr (p<O.OI). The chemokine MIP-l a was expressed at low levels in all samples. CONCLUSIONS: HIV is characterized by a significant degree of mucosal inflammation. Our findings show that the levels of chemokines and chemokine receptors in HIV are similar to those levels seen in active IBD and are significantly higher than those from IBDr and healthy controls. This suggests that the inflammatory response in HIV is at least as potent as in IBD. Topical anti-inflammatories lead to remission and reduction in soluble and cellular markers of inflammation in IBD. Given the presence of marked inflammation, further investigation of the role of adjunctive treatment of HIV-patients with local anti-inflammatory drugs targeting the host immune response, deserves attention.