A Loss of Intestinal Fortitude

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Science  19 Jan 2007:
Vol. 315, Issue 5810, pp. 302-303
DOI: 10.1126/science.315.5810.302d

The large-scale and rapid depletion of CD4+ T cells in the weeks after HIV infection occurs predominantly in the gastrointestinal tract. Accompanying this loss is a sustained whole-scale activation of the immune system, which corresponds directly with the eventual progression to AIDS.

Brenchley et al. propose that the two processes are tightly coupled, with impaired intestinal integrity leading to the translocation of gut microbes, or some of their constituent components, which overstimulate the immune system. Circulating levels of bacterial lipopolysaccharide (LPS), which was used as a marker for microbial translocation, were markedly elevated in the sera of chronically infected HIV individuals and in macaques experimentally infected with the simian immunodeficiency virus (SIV). This increase corresponded directly with footprints of immune activation, including circulating cytokines, antibodies to LPS, and immune-cell turnover. In HIV patients undergoing highly active antiretroviral therapy, LPS levels were decreased, with a corresponding rebound in CD4+ T cell numbers. Furthermore, in the absence of pathology—as typified in the infection of natural primate hosts for SIV—signs of substantial microbial translocation or immune activation were not apparent. The link between HIV infection, integrity of the mucosal immune system, and chronic peripheral immune activation may prove important to consider in future therapies for HIV infection. — SJS

Nat. Med. 12, 1365 (2006).

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