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

Jason M. Brenchley, David A. Price, Timothy W. Schacker, Tedi E. Asher, Guido Silvestri, Srinivas Rao, Zachary Kazzaz, Ethan Bornstein, Olivier Lambotte, Daniel Altmann, Bruce R. Blazar, Benigno Rodriguez, Leia Teixeira-Johnson, Alan Landay, Jeffrey N. Martin, Frederick M. Hecht, Louis J. Picker, Michael M. Lederman, Steven G. Deeks, Daniel C. Douek

Research output: Contribution to journalArticle

2303 Scopus citations

Abstract

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, probably derived from the gastrointestinal tract, are a cause of HIV-related systemic immune activation. Circulating lipopolysaccharide, which we used as an indicator of microbial translocation, was significantly increased in chronically HIV-infected individuals and in simian immunodeficiency virus (SIV)-infected rhesus macaques (P ≤ 0.002). We show that increased lipopolysaccharide is bioactive in vivo and correlates with measures of innate and adaptive immune activation. Effective antiretroviral therapy seemed to reduce microbial translocation partially. Furthermore, in nonpathogenic SIV infection of sooty mangabeys, microbial translocation did not seem to occur. These data establish a mechanism for chronic immune activation in the context of a compromised gastrointestinal mucosal surface and provide new directions for therapeutic interventions that modify the consequences of acute HIV infection.

Original languageEnglish (US)
Pages (from-to)1365-1371
Number of pages7
JournalNature medicine
Volume12
Issue number12
DOIs
StatePublished - Dec 1 2006

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Brenchley, J. M., Price, D. A., Schacker, T. W., Asher, T. E., Silvestri, G., Rao, S., Kazzaz, Z., Bornstein, E., Lambotte, O., Altmann, D., Blazar, B. R., Rodriguez, B., Teixeira-Johnson, L., Landay, A., Martin, J. N., Hecht, F. M., Picker, L. J., Lederman, M. M., Deeks, S. G., & Douek, D. C. (2006). Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nature medicine, 12(12), 1365-1371. https://doi.org/10.1038/nm1511