02060nas a2200325   4500000000100000008004100001653001200042653002100054653001100075653002600086653002800112653000900140653000900149653002400158653001800182653003800200653001500238653003500253653002500288100001400313700001200327700001400339700001300353700001400366245011500380300001200495490000700507520120600514022001401720       2012                            d10aAnimals10aChemokine CXCL1010aFemale10aMacrophage Activation10aMacrophages, Peritoneal10aMale10aMice10aMice, Inbred BALB C10aMycobacterium10aMyeloid Differentiation Factor 8810aNF-kappa B10aNod2 Signaling Adaptor Protein10aToll-Like Receptor 21 aPandey RK1 aSodhi A1 aBiswas SK1 aDahiya Y1 aDhillon M00aMycobacterium indicus pranii mediates macrophage activation through TLR2 and NOD2 in a MyD88 dependent manner.  a5748-540 v303 a<p>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.</p>
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