Publication in detail

Nat Immunol 2008 Dec;9(12):1399-406. Epub 2008 No

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

Basaraba, RJ; Bogdan, C; El, Kasmi KC; Fitzgerald, KA; Henao-Tamayo, M; Kanneganti, TD; Kaplan, G; König, T; Koo, MS; Murray, PJ.; Orme, IM; Pesce, JT; Qualls, JE; Schleicher, U; Smith, AM; Thompson, RW; Tuomanen, EI; Wynn, TA

Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38015, USA.

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 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.

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