Experimental colitis in SIV-uninfected rhesus macaques recapitulates important features of pathogenic SIV infection
Open Access
- 18 August 2015
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 6 (1), 8020
- https://doi.org/10.1038/ncomms9020
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.This publication has 61 references indexed in Scilit:
- UCHIME improves sensitivity and speed of chimera detectionBioinformatics, 2011
- Higher Levels of CRP, D-dimer, IL-6, and Hyaluronic Acid Before Initiation of Antiretroviral Therapy (ART) Are Associated With Increased Risk of AIDS or DeathThe Journal of Infectious Diseases, 2011
- Lipopolysaccharide exposure is linked to activation of the acute phase response and growth failure in pediatric Crohnʼs disease and murine colitisInflammatory Bowel Diseases, 2010
- Compromised gastrointestinal integrity in pigtail macaques is associated with increased microbial translocation, immune activation, and IL-17 production in the absence of SIV infectionMucosal Immunology, 2010
- Where the Wild Things Are: Pathogenesis of SIV Infection in African Nonhuman Primate HostsCurrent HIV/AIDS Reports, 2010
- Simian immunodeficiency virus–induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gutNature Medicine, 2008
- HIV infection and the gastrointestinal immune systemMucosal Immunology, 2007
- Unravelling the pathogenesis of inflammatory bowel diseaseNature, 2007
- Chemically induced mouse models of intestinal inflammationNature Protocols, 2007
- Microbial translocation is a cause of systemic immune activation in chronic HIV infectionNature Medicine, 2006