Experimental colitis in SIV-uninfected rhesus macaques recapitulates important features of pathogenic SIV infection
Year: 2015
Type: article
Abstract: Mucosal damage to the gastrointestinal (GI) tract with resulting microbial translocation is hypothesized to significantly contribute to the heightened and persistent chronic inflammation and immune activation characteristic to HIV infection. Here we employ a non-human primate model of chemically induced colitis in SIV-uninfected rhesus macaques that we developed using dextran sulfate sodium (DSS), to directly test this hypothesis. DSS treatment results in GI barrier damage with associated microbial translocation, inflammation and immune activation. The progression and severity of colitis are longitudinally monitored by a magnetic resonance imaging approach. DSS treatment of SIV-infected African green monkeys, a natural host species for SIV that does not manifest GI tract damage or chronic immune activation during infection, results in colitis with elevated levels of plasma SIV RNA, sCD14, LPS, CRP and mucosal CD4+ T-cell loss. Together these results support the hypothesis that GI tract damage leading to local and systemic microbial translocation, and associated immune activation, are important determinants of AIDS pathogenesis.
Source: Nature Communications
DOI: 10.1038/ncomms9020
Authors: Xing Pei Hao, Carissa M. Lucero, Baris Turkbey, Marcelino L. Bernardo, David R. Morcock, Claire Deleage, Charles M. Trubey, Jeremy Smedley, Nichole R. Klatt, Luis D. Giavedoni, Jan Kristoff, Amy Xu, Gregory Q. Del Prete, Brandon F. Keele, Srinivas S. Rao, W. Gregory Alvord, Peter L. Choyke, Jeffrey D. Lifson, Jason M. Brenchley, Cristian Apetrei, Ivona Pandrea, Jacob D. Estes
Institutions: Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc. (United States), National Cancer Institute, University of Washington, Texas Biomedical Research Institute, University of Pittsburgh, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Vaccine Research Center, Data Management Services (United States)
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: U.S. Department of Health and Human Services, Frederick National Laboratory for Cancer Research, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Center for Research Resources, NHLBI Division of Intramural Research
OpenAlex ID: W2410625873