Intestinal proteomic analysis of a novel non-human primate model of experimental colitis reveals signatures of mitochondrial and metabolic dysfunction

Peter McQueen, Kathleen Busman-Sahay, Florian Rieder, Laura Noël-Romas, Stuart McCorrister, Garrett Westmacott, Jacob Estes, Adam Burgener

Research output: Contribution to journalArticle

Abstract

Animal models recapitulating features of chronic colitis, such as ulcerative colitis, Crohn’s disease, or HIV infection, are critical to study disease pathogenesis and test novel therapeutics. In this study, we used a proteomics approach to explore the molecular intestinal response in two rhesus macaque (RM) animal models of experimentally induced colitis using dextran sulfate sodium (DSS) and simian immunodeficiency virus (SIV) infection. Proteomic analysis detected more than 2500 proteins in colonic tissue collected from 30 RMs. Differential protein expression analysis revealed a protein expression pattern in DSS-treated RMs resembling the proteome of human ulcerative colitis. In a group of 12 DSS-treated RMs compared to 6 with no treatment, decrease in expression of proteins related to mitochondrial energy metabolism, including fatty acid metabolism was noted, while innate immune activation pathways, including complement and coagulation proteins were upregulated. SIV infection of RMs resulted in increased innate immune responses related to viral defense. Proteomic signatures of barrier damage were apparent in both DSS treatment or SIV infection. These results demonstrate that DSS treatment in a non-human primate model resembles features of human ulcerative colitis, making this a promising tool to study important immunological mechanisms in inflammatory bowel disease.

Original languageEnglish (US)
JournalMucosal Immunology
DOIs
StateAccepted/In press - Jan 1 2019

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Dextran Sulfate
Colitis
Proteomics
Primates
Theoretical Models
Simian Immunodeficiency Virus
Virus Diseases
Ulcerative Colitis
Proteins
Animal Models
Proteome
Macaca mulatta
Inflammatory Bowel Diseases
Innate Immunity
Crohn Disease
Energy Metabolism
HIV Infections
Complement System Proteins
Fatty Acids

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Intestinal proteomic analysis of a novel non-human primate model of experimental colitis reveals signatures of mitochondrial and metabolic dysfunction. / McQueen, Peter; Busman-Sahay, Kathleen; Rieder, Florian; Noël-Romas, Laura; McCorrister, Stuart; Westmacott, Garrett; Estes, Jacob; Burgener, Adam.

In: Mucosal Immunology, 01.01.2019.

Research output: Contribution to journalArticle

McQueen, Peter ; Busman-Sahay, Kathleen ; Rieder, Florian ; Noël-Romas, Laura ; McCorrister, Stuart ; Westmacott, Garrett ; Estes, Jacob ; Burgener, Adam. / Intestinal proteomic analysis of a novel non-human primate model of experimental colitis reveals signatures of mitochondrial and metabolic dysfunction. In: Mucosal Immunology. 2019.
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