M. fortuitum-induced CNS-pathology: Deciphering the role of canonical Wnt signaling, blood brain barrier components and cytokines.
Adherens Junctions
/ genetics
Animals
Axin Protein
/ metabolism
Blood-Brain Barrier
/ metabolism
Brain
/ microbiology
Calpain
/ metabolism
Cytokines
/ metabolism
Fish Diseases
/ immunology
Glycogen Synthase Kinase 3 beta
/ metabolism
Interferon-gamma
/ immunology
Interleukin-10
/ immunology
Interleukin-4
/ immunology
Low Density Lipoprotein Receptor-Related Protein-5
/ metabolism
Low Density Lipoprotein Receptor-Related Protein-6
/ metabolism
Mycobacterium Infections, Nontuberculous
/ pathology
Mycobacterium fortuitum
/ immunology
Receptors, Cell Surface
/ metabolism
Th1 Cells
/ immunology
Th2 Cells
/ immunology
Tight Junctions
/ genetics
Tumor Necrosis Factor-alpha
/ immunology
Wnt Proteins
/ metabolism
Wnt Signaling Pathway
/ immunology
Wnt3A Protein
/ metabolism
Zebrafish
/ immunology
Zebrafish Proteins
/ metabolism
beta Catenin
/ metabolism
CNS-pathology
Cytokines
Mycobacterium fortuitum
Wnt-signaling
Zebrafish
Journal
Developmental and comparative immunology
ISSN: 1879-0089
Titre abrégé: Dev Comp Immunol
Pays: United States
ID NLM: 7708205
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
10
12
2020
revised:
24
04
2021
accepted:
24
04
2021
pubmed:
3
5
2021
medline:
3
3
2022
entrez:
2
5
2021
Statut:
ppublish
Résumé
Molecular underpinning of mycobacteria-induced CNS-pathology is not well understood. In the present study, zebrafish were infected with Mycobacterium fortuitum and the prognosis of CNS-pathogenesis studied. We observed M. fortuitum triggers extensive brain-pathology. Evans blue extravasation demonstrated compromised blood-brain barrier (BBB) integrity. Further, decreased expression in tight-junction (TJ) and adherens junction complex (AJC) genes were noted in infected brain. Wnt-signaling has emerged as a major player in host-mycobacterial immunity but its involvement/role in brain-infection is not well studied. Sustained expression of wnt2, wnt3a, fzd5, lrp5/6 and β-catenin, with concordant decline in degradation complex components axin, gsk3β and β-catenin regulator capn2a were observed. The surge in ifng1 and tnfa expression preceding il10 and il4 suggested cytokine-interplay critical in M. fortuitum-induced brain-pathology. Therefore, we suggest adult zebrafish as a viable model for studying CNS-pathology and using the same, conclude that M. fortuitum infection is associated with repressed TJ-AJC gene expression and compromised BBB permeability. Our results implicate Wnt/β-catenin pathway in M. fortuitum-induced CNS-pathology wherein Th1-type signals facilitate bacterial clearance and Th2-type signals prevent the disease sequel.
Identifiants
pubmed: 33933535
pii: S0145-305X(21)00119-1
doi: 10.1016/j.dci.2021.104111
pii:
doi:
Substances chimiques
Axin Protein
0
Cytokines
0
Low Density Lipoprotein Receptor-Related Protein-5
0
Low Density Lipoprotein Receptor-Related Protein-6
0
Receptors, Cell Surface
0
Tumor Necrosis Factor-alpha
0
Wnt Proteins
0
Wnt3A Protein
0
Wnt3a protein, zebrafish
0
Zebrafish Proteins
0
axin2 protein, zebrafish
0
beta Catenin
0
ctnnb1 protein, zebrafish
0
fzd5 protein, zebrafish
0
wnt2ba protein, zebrafish
0
Interleukin-10
130068-27-8
Interleukin-4
207137-56-2
Interferon-gamma
82115-62-6
Glycogen Synthase Kinase 3 beta
EC 2.7.11.1
Calpain
EC 3.4.22.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104111Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.