PUBLICATION
M. fortuitum-induced CNS-pathology: Deciphering the role of canonical Wnt signaling, blood brain barrier components and cytokines
- Authors
- Sharma, S., Kumar, M., Kumar, J., Srivastava, N., Hussain, M.A., Shelly, A., Mazumder, S.
- ID
- ZDB-PUB-210504-2
- Date
- 2021
- Source
- Developmental and comparative immunology 122: 104111 (Journal)
- Registered Authors
- Keywords
- CNS-pathology, Cytokines, Mycobacterium fortuitum, Wnt-signaling, Zebrafish
- MeSH Terms
-
- Adherens Junctions/genetics
- Animals
- Axin Protein/metabolism
- Blood-Brain Barrier/metabolism
- Blood-Brain Barrier/microbiology*
- Brain/microbiology
- Brain/pathology*
- Calpain/metabolism
- Cytokines/metabolism*
- Fish Diseases/immunology*
- Fish Diseases/microbiology
- 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 Infections, Nontuberculous/veterinary
- Mycobacterium fortuitum/immunology*
- Mycobacterium fortuitum/pathogenicity
- 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/microbiology
- Zebrafish Proteins/metabolism
- beta Catenin/metabolism
- PubMed
- 33933535 Full text @ Dev. Comp. Immunol.
Citation
Sharma, S., Kumar, M., Kumar, J., Srivastava, N., Hussain, M.A., Shelly, A., Mazumder, S. (2021) M. fortuitum-induced CNS-pathology: Deciphering the role of canonical Wnt signaling, blood brain barrier components and cytokines. Developmental and comparative immunology. 122:104111.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping