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 language | English (US) |
|---|---|
| Article number | 8020 |
| Journal | Nature Communications |
| Volume | 6 |
| DOIs | |
| State | Published - Aug 18 2015 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Chemistry(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)
Cite this
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; 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 journal › Article
}
TY - JOUR
T1 - Experimental colitis in SIV-uninfected rhesus macaques recapitulates important features of pathogenic SIV infection
AU - Hao, Xing Pei
AU - Lucero, Carissa M.
AU - Turkbey, Baris
AU - Bernardo, Marcelino L.
AU - Morcock, David R.
AU - Deleage, Claire
AU - Trubey, Charles M.
AU - Smedley, Jeremy
AU - Klatt, Nichole
AU - Giavedoni, Luis D.
AU - Kristoff, Jan
AU - Xu, Amy
AU - Del Prete, Gregory Q.
AU - Keele, Brandon F.
AU - Rao, Srinivas S.
AU - Alvord, W. Gregory
AU - Choyke, Peter L.
AU - Lifson, Jeffrey D.
AU - Brenchley, Jason M.
AU - Apetrei, Cristian
AU - Pandrea, Ivona
AU - Estes, Jacob D.
PY - 2015/8/18
Y1 - 2015/8/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84939515008&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84939515008&partnerID=8YFLogxK
U2 - 10.1038/ncomms9020
DO - 10.1038/ncomms9020
M3 - Article
C2 - 26282376
AN - SCOPUS:84939515008
VL - 6
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 8020
ER -