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

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

doi:10.1038/nm1511

Cited by 3,559HIV Research and TreatmentHIV-related health complications and treatmentsHIV/AIDS Research and Interventions

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

Brenchley, Jason M, Price, David A, Schacker, Timothy W, Asher, Tedi E, Silvestri, Guido, Rao, Srinivas, Kazzaz, Zachary, Bornstein, Ethan +12 more·2006·Nature Medicine

DOI 10.1038/nm1511

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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 <or= 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.

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Chronic inflammation in HIV is mediated by depletion of memory CD4+ T cells, resulting in increased permeability in the gut epithelium and translocation of microbial products into the circulation, which causes inflammation.
“Chronic inflammation in HIV is mediated by depletion of memory CD41+ T cells, resulting in increased permeability in the gut epithelium and translocation of microbial products into the circulation, which causes inflammation136.”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [136]
Blood endotoxin levels are elevated during infections, gut inflammation, gum disease, and neurodegenerative disease.
“but are elevated during infections, gut inflammation, gum disease and neurodegenerative disease.”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [12]
Peripheral diseases that elevate blood endotoxin, such as sepsis, AIDS and liver failure, also result in neurodegeneration.
“Peripheral diseases that elevate blood endotoxin, such as sepsis, AIDS and liver failure, also result in neurodegeneration.”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [12]
Plasma endotoxin levels are increased in AIDS, HIV-infected patients and SIV-infected rhesus macaques, as a result of gut-wall damage.
“Plasma endotoxin levels are increased in AIDS, HIV-infected patients and SIV-infected rhesus macaques, as a result of gut-wall damage [12].”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [12]

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Authors: 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.
Affiliations: National Institutes of Health (US)
University of Minnesota (US)
University of Pennsylvania (US)
Assistance Publique – Hôpitaux de Paris (FR)
Hammersmith Hospital (GB)
University Hospitals of Cleveland (US)
Rush University Medical Center (US)
University of California, San Francisco (US)
Oregon Health & Science University (US)
Corresponding author: Douek, Daniel C
ORCID: Brenchley, Jason M
Price, David A
Schacker, Timothy W
Silvestri, Guido
Bornstein, Ethan
Lambotte, Olivier
Altmann, Daniel
Blazar, Bruce R
Rodriguez, Benigno
Landay, Alan
Martin, Jeffrey N
Hecht, Frederick M
Picker, Louis J
Lederman, Michael M
Deeks, Steven G
Douek, Daniel C
Venue: Nature Medicine
Publisher: Springer Science and Business Media LLC
Published: 2006-11-19
Volume: 12
Issue: 12
Pages: 1365-1371
ISSN: 1078-8956 (ISSN-L)
1546-170X
DOI: 10.1038/nm1511
OpenAlex: W2122483069
Cited by: 3,559
References: 52
Citations by year: 2026: 90 · 2025: 104 · 2024: 134 · 2023: 126 · 2022: 125 · 2021: 157 · 2020: 166 · 2019: 214 · 2018: 178 · 2017: 170 · 2016: 221 · 2015: 232 · 2014: 255 · 2013: 254 · 2012: 253
FWCI: 46.88
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (2m01rr000083-41)
Oregon National Primate Research Center
Yerkes National Primate Research Center, Emory University
National Institute of Mental Health (P30-MH62246, P30MH062246)
National Institute of Allergy and Infectious Diseases (AI38858, AI 41531, P30-AI-27763, AI36219, R0I AI052755, AI 066998, AI052745, U01AI038858, R01AI052745, U01AI025879, U01AI041531, AI 25879, P30AI036219, P30AI027763)
National Center for Research Resources (RR-00 165, M01-RR0083-37, P51RR000165)
Topics: Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Health Sciences › Medicine › Emergency Medicine › HIV-related health complications and treatments
Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
Keywords: microbial translocation, chronic HIV infection, systemic immune activation, lipopolysaccharide, intestinal barrier dysfunction, gastrointestinal tract, simian immunodeficiency virus, rhesus monkeys, sooty mangabey, antiretroviral therapy, acute HIV infection
MeSH terms: Animals, Chronic Disease, Enterobacteriaceae, Feces, Humans, Immune System, Lipopolysaccharides, Macaca mulatta, Simian Immunodeficiency Virus, HIV-1, HIV Infections, Cercocebus atys, Bacterial Translocation, Anti-HIV Agents, Antiretroviral Therapy, Highly Active

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

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