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Mycobacterium tuberculosis Rv1096, facilitates mycobacterial survival by modulating the NF-κB/MAPK pathway as peptidoglycan N-deacetylase
- Source :
- Molecular immunology. 127
- Publication Year :
- 2019
-
Abstract
- Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that can infect and replicate in macrophages. Peptidoglycan (PGN) is a major component of the mycobacterial cell wall and is recognized by host pattern recognition receptors (PRRs). Many bacteria modulate and evade the immune defenses of their hosts through PGN deacetylation. Rv1096 was previously characterized as a PGN N-deacetylase gene in Mtb. However, the underlying mechanism by which Rv1096 regulates host immune defenses during macrophage infection remains unclear. In the present study, we investigated the role of Rv1096 in evading host immunity using a recombinant M. smegmatis expressing exogenous Rv1096 and Rv1096-deleted Mtb strain H37Rv mutant. We found that Rv1096 promoted intracellular bacillary survival and inhibited the inflammatory response in M. smegmatis- or Mtb-infected macrophages. The inhibition of mycobacteria-induced inflammatory response in macrophages was at least partially due to NF-κB and MAPK activation downstream of TLR and NOD signaling pathways. Furthermore, we found that Rv1096 inhibitory effect on inflammatory response was associated with TLR2, TLR4 and NOD2. Finally, we demonstrated the PGN deacetylase activity of Rv1096 by Fourier transform IR and Rv1096 NODB deficient mutant. Our findings suggest that Rv1096 may deacetylate PGNs to evade PRRs recognition, thus protecting Mtb from host immune surveillance and clearance in macrophages.
- Subjects :
- 0301 basic medicine
MAP Kinase Signaling System
Immunology
Mycobacterium smegmatis
Peptidoglycan
Biology
Microbiology
Amidohydrolases
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Immune system
Bacterial Proteins
Protein Domains
NOD2
Animals
Molecular Biology
Inflammation
Microbial Viability
Macrophages
Pattern recognition receptor
NF-kappa B
NF-κB
Mycobacterium tuberculosis
Mice, Inbred C57BL
TLR2
030104 developmental biology
RAW 264.7 Cells
chemistry
TLR4
Cytokines
Female
Inflammation Mediators
030215 immunology
Deacetylase activity
Subjects
Details
- ISSN :
- 18729142
- Volume :
- 127
- Database :
- OpenAIRE
- Journal :
- Molecular immunology
- Accession number :
- edsair.doi.dedup.....bc9f89cc2d572f66256a3ca70509bc3f