Toll-like receptor-induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens

作者：El Kasmi Karim C; Qualls Joseph E; Pesce John T; Smith Amber M; Thompson Robert W; Henao Tamayo Marcela; Basaraba Randall J; Koenig Till; Schleicher Ulrike; Koo Mi Sun; Kaplan Gilla; Fitzgerald Katherine A; Tuomanen Elaine I; Orme Ian M; Kanneganti Thirumala Devi; Bogdan Christian; Wynn Thomas A; Murray Peter J^*

来源：Nature Immunology, 2008, 9(12): 1399-1406.

DOI：10.1038/ni.1671

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 contrast 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.

• 出版日期2008-12
• 单位河北医科大学