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; Ivona Pandrea; Jacob D Estes

doi:10.1038/ncomms9020

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 ApetreiIvona Pandrea, Jacob D Estes

Research output: Contribution to journal › Article › peer-review

54 Scopus citations

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)
Pages (from-to)	8020
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms9020
State	Published - Aug 18 2015
Externally published	Yes

Keywords

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

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access

10.1038/ncomms9020

OpenUrl availability

Full text

Cite this

Hao, X. P., Lucero, C. M., Turkbey, B., Bernardo, M. L., Morcock, D. R., Deleage, C., Trubey, C. M., Smedley, J., Klatt, N. R., Giavedoni, L. D., Kristoff, J., Xu, A., Del Prete, G. Q., Keele, B. F., Rao, S. S., Alvord, W. G., Choyke, P. L., Lifson, J. D., Brenchley, J. M., ... 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

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, pp. 8020. https://doi.org/10.1038/ncomms9020

@article{0aa133151ca54f2393aafdff1984be48,

title = "Experimental colitis in SIV-uninfected rhesus macaques recapitulates important features of pathogenic SIV infection",

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. ",

keywords = "Animals, Colitis/chemically induced, Dextran Sulfate/toxicity, Female, Gastrointestinal Tract/pathology, Macaca mulatta, Male, Simian Acquired Immunodeficiency Syndrome/pathology, Simian Immunodeficiency Virus",

author = "Hao, {Xing Pei} and Lucero, {Carissa M} and Baris Turkbey and Bernardo, {Marcelino L} and Morcock, {David R} and Claire Deleage and Trubey, {Charles M} and Jeremy Smedley and Klatt, {Nichole R} and Giavedoni, {Luis D} and Jan Kristoff and Amy Xu and {Del Prete}, {Gregory Q} and Keele, {Brandon F} and Rao, {Srinivas S} and Alvord, {W Gregory} and Choyke, {Peter L} and Lifson, {Jeffrey D} and Brenchley, {Jason M} and Cristian Apetrei and Ivona Pandrea and Estes, {Jacob D}",

year = "2015",

month = aug,

day = "18",

doi = "10.1038/ncomms9020",

language = "English (US)",

volume = "6",

pages = "8020",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

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 R

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.

KW - Animals

KW - Colitis/chemically induced

KW - Dextran Sulfate/toxicity

KW - Female

KW - Gastrointestinal Tract/pathology

KW - Macaca mulatta

KW - Male

KW - Simian Acquired Immunodeficiency Syndrome/pathology

KW - Simian Immunodeficiency Virus

U2 - 10.1038/ncomms9020

DO - 10.1038/ncomms9020

M3 - Article

C2 - 26282376

SN - 2041-1723

VL - 6

SP - 8020

JO - Nature communications

JF - Nature communications

ER -

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

Abstract

Keywords

PubMed: MeSH publication types

UN SDGs

Access

OpenUrl availability

Fingerprint

Cite this