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

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 & 2 others Ivona Pandrea, Jacob D. Estes

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish (US)
Article number8020
JournalNature Communications
Volume6
DOIs
StatePublished - Aug 18 2015
Externally publishedYes

Fingerprint

Dextran Sulfate
infectious diseases
Colitis
Macaca mulatta
dextrans
Gastrointestinal Tract
Chemical activation
sodium sulfates
activation
damage
Infection
Inflammation
Cercopithecus aethiops
acquired immunodeficiency syndrome
primates
monkeys
pathogenesis
Primates
human immunodeficiency virus
HIV Infections

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Hao, X. P., Lucero, C. M., Turkbey, B., Bernardo, M. L., Morcock, D. R., Deleage, C., ... Estes, J. D. (2015). Experimental colitis in SIV-uninfected rhesus macaques recapitulates important features of pathogenic SIV infection. Nature Communications, 6, [8020]. https://doi.org/10.1038/ncomms9020

Experimental colitis in SIV-uninfected rhesus macaques recapitulates important features of pathogenic SIV infection. / Hao, Xing Pei; Lucero, Carissa M.; Turkbey, Baris; Bernardo, Marcelino L.; Morcock, David R.; Deleage, Claire; Trubey, Charles M.; Smedley, Jeremy; Klatt, Nichole R.; Giavedoni, Luis D.; Kristoff, Jan; Xu, Amy; Del Prete, Gregory Q.; Keele, Brandon F.; Rao, Srinivas S.; Alvord, W. Gregory; Choyke, Peter L.; Lifson, Jeffrey D.; Brenchley, Jason M.; Apetrei, Cristian; Pandrea, Ivona; Estes, Jacob D.

In: Nature Communications, Vol. 6, 8020, 18.08.2015.

Research output: Contribution to journalArticle

Hao, XP, Lucero, CM, Turkbey, B, Bernardo, ML, Morcock, DR, Deleage, C, Trubey, CM, Smedley, J, Klatt, NR, Giavedoni, LD, Kristoff, J, Xu, A, Del Prete, GQ, Keele, BF, Rao, SS, Alvord, WG, Choyke, PL, Lifson, JD, Brenchley, JM, Apetrei, C, Pandrea, I & Estes, JD 2015, 'Experimental colitis in SIV-uninfected rhesus macaques recapitulates important features of pathogenic SIV infection', Nature Communications, vol. 6, 8020. https://doi.org/10.1038/ncomms9020
Hao, Xing Pei ; Lucero, Carissa M. ; Turkbey, Baris ; Bernardo, Marcelino L. ; Morcock, David R. ; Deleage, Claire ; Trubey, Charles M. ; Smedley, Jeremy ; Klatt, Nichole R. ; Giavedoni, Luis D. ; Kristoff, Jan ; Xu, Amy ; Del Prete, Gregory Q. ; Keele, Brandon F. ; Rao, Srinivas S. ; Alvord, W. Gregory ; Choyke, Peter L. ; Lifson, Jeffrey D. ; Brenchley, Jason M. ; Apetrei, Cristian ; Pandrea, Ivona ; Estes, Jacob D. / Experimental colitis in SIV-uninfected rhesus macaques recapitulates important features of pathogenic SIV infection. In: Nature Communications. 2015 ; Vol. 6.
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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.",
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