Identification, Characterization, and Transcriptional Reprogramming of Epithelial Stem Cells and Intestinal Enteroids in Simian Immunodeficiency Virus Infected Rhesus Macaques.
Animals
Cellular Reprogramming
/ genetics
Epithelial Cells
/ metabolism
Female
Gene Expression Profiling
/ methods
Gene Ontology
Host-Pathogen Interactions
Intestine, Small
/ metabolism
Macaca mulatta
/ genetics
Male
Organoids
/ metabolism
RNA-Seq
/ methods
Signal Transduction
/ genetics
Simian Acquired Immunodeficiency Syndrome
/ genetics
Simian Immunodeficiency Virus
/ physiology
Stem Cells
/ metabolism
Viral Load
LGR5
SIV
alpha defensin
epithelial cells
intestinal stem cell (ISC)
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
03
09
2021
accepted:
02
11
2021
entrez:
10
12
2021
pubmed:
11
12
2021
medline:
15
2
2022
Statut:
epublish
Résumé
Epithelial cell injury and impaired epithelial regeneration are considered key features in HIV pathogenesis and contribute to HIV-induced generalized immune activation. Understanding the molecular mechanisms underlying the disrupted epithelial regeneration might provide an alternative approach for the treatment of HIV-mediated enteropathy and immune activation. We have observed a significant increased presence of α defensin5+ (HD5) Paneth cells and proliferating Ki67+ epithelial cells as well as decreased expression of E-cadherin expression in epithelial cells during SIV infection. SIV infection did not significantly influence the frequency of LGR5+ stem cells, but the frequency of HD5+ cells was significantly higher compared to uninfected controls in jejunum. Our global transcriptomics analysis of enteroids provided novel information about highly significant changes in several important pathways like metabolic, TCA cycle, and oxidative phosphorylation, where the majority of the differentially expressed genes were downregulated in enteroids grown from chronically SIV-infected macaques compared to the SIV-uninfected controls. Despite the lack of significant reduction in LGR5+ stem cell population, the dysregulation of several intestinal stem cell niche factors including Notch, mTOR, AMPK and Wnt pathways as well as persistence of inflammatory cytokines and chemokines and loss of epithelial barrier function in enteroids further supports that SIV infection impacts on epithelial cell proliferation and intestinal homeostasis.
Identifiants
pubmed: 34887863
doi: 10.3389/fimmu.2021.769990
pmc: PMC8650114
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
769990Subventions
Organisme : NIH HHS
ID : P51 OD011104
Pays : United States
Organisme : NCRR NIH HHS
ID : P51 RR000164
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK109883
Pays : United States
Informations de copyright
Copyright © 2021 Boby, Cao, Ransom, Pace, Mabee, Shroyer, Das, Didier, Srivastav, Porter, Sha and Pahar.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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