Toll-like receptor-induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens.
Journal:
Nat. Immunol. 2008 DecAuthors:
El Kasmi KC, Qualls JE, Pesce JT, Smith AM, Thompson RW, Henao-Tamayo M, Basaraba RJ, König T, Schleicher U, Koo MS, Kaplan G, Fitzgerald KA, Tuomanen EI, Orme IM, Kanneganti TD, Bogdan C, Wynn TA, Murray PJ
Abstract
Toll-like receptor (TLR) signaling in macrophages is required for antipathogen responses, including the biosynthesis of nitric oxide from arginine, and is essential for immunity to Mycobacterium tuberculosis, Toxoplasma gondii and other intracellular pathogens. Here we report a 'loophole' in the TLR pathway that is advantageous to these pathogens. Intracellular pathogens induced expression of the arginine hydrolytic enzyme arginase 1 (Arg1) in mouse macrophages through the TLR pathway. In contra
...[more]st to diseases dominated by T helper type 2 responses in which Arg1 expression is greatly increased by interleukin 4 and 13 signaling through the transcription factor STAT6, TLR-mediated Arg1 induction was independent of the STAT6 pathway. Specific elimination of Arg1 in macrophages favored host survival during T. gondii infection and decreased lung bacterial load during tuberculosis infection.[less]
Mesh Headings:
Animals, Arginase, Bacterial Infections, CCAAT-Enhancer-Binding Protein-beta, Immunoblotting, Immunohistochemistry, Macrophages, Mice, Mice, Knockout, Myeloid Differentiation Factor 88, STAT6 Transcription Factor, Toll-Like Receptors