Experimental colitis in SIV-uninfected rhesus macaques recapitulates important features of pathogenic SIV infection

Nat Commun. 2015 Aug 18;6:8020. doi: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Colitis / chemically induced*
  • Colitis / pathology*
  • Dextran Sulfate / toxicity
  • Female
  • Gastrointestinal Tract / pathology
  • Macaca mulatta
  • Male
  • Simian Acquired Immunodeficiency Syndrome / pathology*
  • Simian Immunodeficiency Virus*

Substances

  • Dextran Sulfate

Associated data

  • BioProject/PRJNA288157