Microbial Translocation Is Associated with Increased Monocyte Activation and Dementia in AIDS Patients
Open accessAbstract
Elevated plasma lipopolysaccharide (LPS), an indicator of microbial translocation from the gut, is a likely cause of systemic immune activation in chronic HIV infection. LPS induces monocyte activation and trafficking into brain, which are key mechanisms in the pathogenesis of HIV-associated dementia (HAD). To determine whether high LPS levels are associated with increased monocyte activation and HAD, we obtained peripheral blood samples from AIDS patients and examined plasma LPS by Limulus amebocyte lysate (LAL) assay, peripheral blood monocytes by FACS, and soluble markers of monocyte activation by ELISA. Purified monocytes were isolated by FACS sorting, and HIV DNA and RNA levels were quantified by real time PCR. Circulating monocytes expressed high levels of the activation markers CD69 and HLA-DR, and harbored low levels of HIV compared to CD4(+) T-cells. High plasma LPS levels were associated with increased plasma sCD14 and LPS-binding protein (LBP) levels, and low endotoxin core antibody levels. LPS levels were higher in HAD patients compared to control groups, and were associated with HAD independently of plasma viral load and CD4 counts. LPS levels were higher in AIDS patients using intravenous heroin and/or ethanol, or with Hepatitis C virus (HCV) co-infection, compared to control groups. These results suggest a role for elevated LPS levels in driving monocyte activation in AIDS, thereby contributing to the pathogenesis of HAD, and provide evidence that cofactors linked to substance abuse and HCV co-infection influence these processes.
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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 [105]
HIV infection can progress to HIV-associated dementia, and this correlates with plasma endotoxin levels, which may drive monocyte activation and trafficking into the brain.
“HIV infection can progress to HIV-associated dementia, and this correlates with plasma endotoxin levels, which may drive monocyte activation and trafficking into the brain [105].”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [105]
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- Authors
- Ancuta, P., Kamat, A., Kunstman, K. J., Kim, E.-Y., Autissier, P., Wurcel, A., Zaman, T., Stone, D., Mefford, M., Morgello, S., Singer, E. J., Wolinsky, S. M., & Gabuzda, D.
- Affiliations
- Harvard University (US)
- Northwestern University (US)
- Beth Israel Deaconess Medical Center (US)
- Lemuel Shattuck Hospital (US)
- Mount Sinai Hospital (US)
- University of California, Los Angeles (US)
- Corresponding author
- Gabuzda, Dana
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-06-25
- Volume
- 3
- Issue
- 6
- Pages
- e2516
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2424175
- OpenAlex
- W2162723667
- Cited by
- 499
- References
- 64
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 26 · 2023: 15 · 2022: 15 · 2021: 14 · 2020: 30 · 2019: 40 · 2018: 27 · 2017: 22 · 2016: 34 · 2015: 25 · 2014: 53 · 2013: 36 · 2012: 41
- FWCI
- 12.47
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Dana-Farber Cancer Institute
- Institut National de la Santé et de la Recherche Médicale
- National Institutes of Health
- Center for AIDS Research, University of Washington
- National Institute of Mental Health (R01MH083588, R24MH059656, MH59745, U01MH083545, MH083588, R24MH059724, R24MH059745, MH59656, MH 59724)
- National Institute on Drug Abuse (R01DA016549, R21DA026322, DA 016549)
- National Institute of Neurological Disorders and Stroke (NS 38841, R24NS038841, NS54591, NS060611)
- 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 › Surgery › Infectious Diseases and Tuberculosis
- Keywords
- microbial translocation, lipopolysaccharide, HIV-associated dementia, monocyte activation, AIDS, systemic immune activation, CD69, HLA-DR, soluble CD14, LPS-binding protein, endotoxin core antibody, heroin use, hepatitis C coinfection, gut-brain axis
- MeSH terms
- Acquired Immunodeficiency Syndrome, Cell Separation, DNA, Viral, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, HIV, Humans, Lipopolysaccharides, Lymphocyte Activation, Monocytes, RNA, Viral, Virus Replication, CD4-Positive T-Lymphocytes, AIDS Dementia Complex, Polymerase Chain Reaction
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