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Publication : Role of TLR2- and TLR4-mediated signaling in Mycobacterium tuberculosis-induced macrophage death.

First Author  Sánchez D Year  2010
Journal  Cell Immunol Volume  260
Issue  2 Pages  128-36
PubMed ID  19919859 Mgi Jnum  J:155569
Mgi Id  MGI:4414730 Doi  10.1016/j.cellimm.2009.10.007
Citation  Sanchez D, et al. (2010) Role of TLR2- and TLR4-mediated signaling in Mycobacterium tuberculosis-induced macrophage death. Cell Immunol 260(2):128-36
abstractText  Infection of macrophages with Mycobacterium tuberculosis (Mtb) induces cell death by apoptosis or necrosis. TLRs 2 and 4 recognition of mycobacterial ligands has been independently associated to apoptosis induction. To try to understand the particular contribution of these receptors to apoptotic or necrotic signaling upon infection with live Mtb H37Rv, we used macrophage lines derived from wild-type or TLR2-, TLR4-, and MyD88-deficient mouse strains. Mtb-infection triggered apoptosis depending on a TLR2/TLR4/MyD88/p38/ERK/PI-3K/NF-kB pathway; however, necrosis was favored in absence of TLR4 signaling independently of p38, ERK1/2, PI-3K or NF-kappaB activity. In conclusion, our results indicate that cooperation between TLR2- and TLR4-dependent mediated signals play a critical role in macrophage apoptosis induced by Mtb and the TLR4-mediated signaling has important role in the maintenance of the balance between apoptotic vs. necrotic cell death induced by macrophage infection with Mtb.
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