TY - JOUR
T1 - Intestinal proteomic analysis of a novel non-human primate model of experimental colitis reveals signatures of mitochondrial and metabolic dysfunction
AU - McQueen, Peter
AU - Busman-Sahay, Kathleen
AU - Rieder, Florian
AU - Noël-Romas, Laura
AU - McCorrister, Stuart
AU - Westmacott, Garrett
AU - Estes, Jacob D.
AU - Burgener, Adam
N1 - Publisher Copyright:
© 2019, Society for Mucosal Immunology.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41385-019-0200-2
DO - 10.1038/s41385-019-0200-2
M3 - Article
C2 - 31481749
AN - SCOPUS:85071888756
SN - 1933-0219
VL - 12
SP - 1327
EP - 1335
JO - Mucosal Immunology
JF - Mucosal Immunology
IS - 6
ER -