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Unraveling the relationship between microbial translocation and systemic immune activation in HIV infection
Liang Shan, Robert F. Siliciano
Liang Shan, Robert F. Siliciano
Published May 16, 2014
Citation Information: J Clin Invest. 2014;124(6):2368-2371. https://doi.org/10.1172/JCI75799.
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Commentary

Unraveling the relationship between microbial translocation and systemic immune activation in HIV infection

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Abstract

Chronic immune activation is a key factor in HIV-1 disease progression. The translocation of microbial products from the intestinal lumen into the systemic circulation occurs during HIV-1 infection and is associated closely with immune activation; however, it has not been determined conclusively whether microbial translocation drives immune activation or occurs as a consequence of HIV-1 infection. In an important study in this issue of the JCI, Kristoff and colleagues describe the role of microbial translocation in producing immune activation in an animal model of HIV-1 infection, SIV infection of pigtailed macaques. Blocking translocation of intestinal bacterial LPS into the circulation dramatically reduced T cell activation and proliferation, production of proinflammatory cytokines, and plasma SIV RNA levels. This study directly demonstrates that microbial translocation promotes the systemic immune activation associated with HIV-1/SIV infection.

Authors

Liang Shan, Robert F. Siliciano

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Figure 1

Microbial translocation and immune activation during HIV-1 infection.

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Microbial translocation and immune activation during HIV-1 infection.
(A...
(A) The intact intestinal epithelium in uninfected individuals. Commensal bacteria and released microbial products, including LPS, are restricted to the gut lumen by a continuous lining of enterocytes. (B) Translocation of commensal bacteria and bacterial products from the gut lumen into the intestinal wall and peripheral blood during HIV-1 infection. HIV-1 infection induces death of intestinal epithelial cells and depletes intestinal CD4+ T cells, particularly Th17 cells. Loss of intestinal epithelial cells allows commensal bacteria to enter intestinal wall. Loss of Th17 cells allows bacterial overgrowth. Translocation of microbial products into peripheral blood causes systemic immune activation. Activated peripheral CD4+ T cells are highly susceptible to HIV-1 infection. (C) The drug sevelamer blocks translocation of bacterial LPS into the systemic circulation, preventing immune activation. Sevelamer binds and sequesters bacterial LPS in intestinal lumen. Blocking bacterial LPS translocation of LPS into the circulation prevents systemic immune activation, leaving the majority of peripheral CD4+ T cells quiescent and unsusceptible to HIV-1 infection.
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