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- W4313366346 abstract "Abstract Macrophages play a major role in the immune system, both as antimicrobial effector cells and as immunoregulatory cells, which induce, suppress or modulate adaptive immune responses. These key aspects of macrophage biology are fundamentally driven by the phenotype of macrophage that is prevalent in an evolving or ongoing immune response. One of the PE family proteins, PE11 (LipX or Rv1169c), demonstrate esterase activity and specific to pathogenic mycobacteria is found to polarize the macrophage towards M2 phenotype. In this study, we report that in macrophages, Msmeg-PE11 down-regulates inducible NO synthase (iNOS) and antimicrobial NO production, but in parallel there is an induction of arginase-I via p38 MAPK activation, and of ornithine decarboxylase (ODC), the first and rate-limiting step in the polyamine synthesis. Furthermore, results revealed that arginase-I regulates Msmeg-PE11 growth directly by affecting the polyamine synthesis in macrophages. These results identify a novel mechanism of immune dysregulation induced by M. tuberculosis lipolytic enzyme PE11 and by targeting PE11 and/or host arginine-polyamine biosynthesis pathway with specific inhibitors could negatively affect M. tuberculosis growth and have a positive impact in the treatment of multi-drug resistant tuberculosis." @default.
- W4313366346 created "2023-01-06" @default.
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- W4313366346 date "2019-05-01" @default.
- W4313366346 modified "2023-09-26" @default.
- W4313366346 title "Arginine-polyamine biosynthesis pathway and mediate bacillary survival in macrophages" @default.
- W4313366346 doi "https://doi.org/10.4049/jimmunol.202.supp.190.57" @default.
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