HIV infection and the gastrointestinal immune system

Abstract

There has recently been a resurgence of interest in the gastrointestinal pathology observed in patients infected with HIV. The gastrointestinal tract is a major site of HIV replication, which results in massive depletion of lamina propria CD4 T cells during acute infection. Highly active antiretroviral therapy leads to incomplete suppression of viral replication and substantially delayed and only partial restoration of gastrointestinal CD4 T cells. The gastrointestinal pathology associated with HIV infection comprises significant enteropathy with increased levels of inflammation and decreased levels of mucosal repair and regeneration. Assessment of gut mucosal immune system has provided novel directions for therapeutic interventions that modify the consequences of acute HIV infection.

Figure 1

HIV-associated damage to the GI tract. (a) A healthy GI tract with villi, crypts, macrophages, dendritic cells, maintenance of the epithelial barrier, T cells, B cells, and luminal defensin peptides. (b) A chronically HIV-infected GI tract with (1) blunted villi, (2) crypt hyperplasia, (3) damage to the epithelial barrier with enterocyte apoptosis, (4) decreased luminal defensin, (5) massive CD4 T-cell depletion, (6) high frequencies of infected CD4 T cells with release of virions, (7) microbial translocation, and (8) increased permeability. (Reprinted from ref 103.)