Mycobacterium indicus pranii mediates macrophage activation through TLR2 and NOD2 in a MyD88 dependent manner.
Mycobacterium indicus pranii (MIP) is a non-pathogenic strain of mycobacterium and has been used as a vaccine against tuberculosis and leprosy. Here, we investigated the role of different pattern recognition receptors in the recognition of heat-killed MIP by macrophages. Treatment of macrophages with MIP caused upregulation of pro-inflammatory cytokines (like TNFα and IL-1β) which was mediated through both TLR2 and NOD2, as revealed by our knockdown and/or knockout studies. Mechanistically, MIP-induced macrophage activation was shown to result in NF-κB activation and drastically abrogated by MyD88 deficiency, suggesting its regulation via an MyD88-dependent, NF-κB pathway. Interestingly, the IFN-inducible cytokine, CXCL10, which is known target of the TRIF-dependent TLR pathway was found to be upregulated in response to MIP but, in an MyD88-dependent manner. Collectively, these results demonstrate macrophages to recognize and respond to MIP through a TLR2, NOD2 and an MyD88-dependent pathway. However, further studies should clarify whether additional TLR-dependent or -independent pathways also exist in regulating the full spectrum of MIP action on macrophage activation.
School of Biotechnology, Faculty of Science, Banaras Hindu University, Varanasi 221005, India.
Rajeev Kumar
RK
Pandey
Ajit
A
Sodhi
Subhra K
SK
Biswas
Yogesh
Y
Dahiya
Manprit K
MK
Dhillon
D000818:Animals; D054357:Chemokine CXCL10 / Q000276:immunology; D005260:Female; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000382:microbiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009161:Mycobacterium / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology; D053473:Nod2 Signaling Adaptor Protein / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology*
D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2