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Microbial translocation is a cause of systemic immune activation in chronic HIV infection

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Chronic activation of the immune system is a hallmark of progressive HIV infection and better predicts disease outcome than plasma viral load, yet its etiology remains obscure. Here, we show that circulating microbial products, likely derived from the gastrointestinal tract, are a primary cause of HIV-related systemic immune activation. Circulating lipopolysaccharide, an indicator of microbial translocation, is significantly increased in chronically HIV-infected individuals and SIV-infected rhesus macaques. We show that monocytes are chronically stimulated in vivo by increased lipopolysaccharide, which also correlates with measures of innate and adaptive immune activation. Effective antiretroviral therapy appears to reduce microbial translocation. Furthermore, in non-pathogenic SIV infection of sooty mangabeys, microbial translocation does not seem to occur. These data establish a mechanism for chronic immune activation in the context of a compromised gastrointestinal mucosal surface and provide novel directions for therapeutic interventions that modify the consequences of acute HIV infection.

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Correspondence to Jason M Brenchley.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Brenchley, J.M. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Retrovirology 3, S98 (2006) doi:10.1186/1742-4690-3-S1-S98

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Keywords

  • Immune Activation
  • Rhesus Macaque
  • Plasma Viral Load
  • Systemic Immune Activation
  • Microbial Translocation