PUBLICATION
miR-146a is Critical for Orchestrating Mycobacterium fortuitum Survival Through Anti-inflammatory and M2 Macrophage Responses in Fish
- Authors
- Mehta, P., Mazumder, S.
- ID
- ZDB-PUB-250315-8
- Date
- 2025
- Source
- Fish & shellfish immunology : 110271110271 (Journal)
- Registered Authors
- Keywords
- Immune evasion, Inflammation, M. fortuitum, Macrophages, Zebrafish, miR-146a
- MeSH Terms
-
- Animals
- Fish Diseases*/genetics
- Fish Diseases*/immunology
- Fish Diseases*/microbiology
- Interleukin-1 Receptor-Associated Kinases/genetics
- Macrophages*/immunology
- MicroRNAs*/genetics
- MicroRNAs*/immunology
- MicroRNAs*/metabolism
- Mycobacterium Infections, Nontuberculous*/genetics
- Mycobacterium Infections, Nontuberculous*/immunology
- Mycobacterium Infections, Nontuberculous*/microbiology
- Mycobacterium Infections, Nontuberculous*/veterinary
- Mycobacterium fortuitum*/physiology
- Zebrafish*/immunology
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 40081436 Full text @ Fish Shellfish Immunol.
Citation
Mehta, P., Mazumder, S. (2025) miR-146a is Critical for Orchestrating Mycobacterium fortuitum Survival Through Anti-inflammatory and M2 Macrophage Responses in Fish. Fish & shellfish immunology. :110271110271.
Abstract
The significance of microRNAs (miRNAs) in host response to non-tuberculoid mycobacteria like Mycobacterium fortuitum remains nascent. Using zebrafish kidney macrophages (ZFKM), we elucidate a novel function of miR-146a, orchestrated by the TLR-2-PI3K-NF-κB pathway, in M. fortuitum pathogenesis. We demonstrate that miR-146a facilitates anti-inflammatory response by targeting IRAK-1 and TRAF-6 in M. fortuitum-infected ZFKM. Moreover, miR-146a mitigates M1 macrophage activity by suppressing the iNOS-NO axis while enhancing M2-specific TGF-β mRNA expression and subsequent inhibition of M. fortuitum eradication. These findings collectively suggest that miR-146a diminishes macrophage-mediate M. fortuitum clearance. Our study provides novel insights into the intricate interplay between miRNAs and mycobacterial infections. We propose a mechanistic model wherein the TLR-2/NF-κB axis initiates miR-146a expression, which, in turn, suppresses irak-1 and traf-6, fostering the development of M2 macrophages. Consequently, this creates an anti-inflammatory environment conducive to M. fortuitum survival. Our findings provide novel insights into the intricate interplay between miRNAs and mycobacterial persistence, a concerning aspect of pathogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping