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

El Kasmi, K. C. et al., Nat. Immunol, 2008, 9: 1399-1406.

Speaker: 李婉綺                                                   Time: 14:10-15:00, 18, Feb., 2009

Commentator: 何漣漪 老師                                Place: Room 601

Abstract:

      In macrophages, Toll-like receptors (TLRs) activate protective immune responses. A key antipathogen effector is nitric oxid (NO) which is required for host control of intracellular infections, including Mycobacterium species, Toxoplasma gondii, Leishmania and other intracellular pathogens¹. It is known that arginine hydrolytic enzyme (arginase) can compete with NO synthases for their common substrate, arginine².  In this study³, a “loophole” in the TLR pathway has been found to be advantageous to the intracellular pathogen, which induced expression of arginase 1 (Arg1) in mouse macrophages through the TLR pathway hence to suppress NO production.  In contrast to diseases dominated by T helper type 2 response in which Arg1 expression is greatly increased by IL-4 and IL-13 signaling through the transcription factor STAT6⁴, TLR-mediated Arg1 induction was independent of the STAT6 pathway but depended on C/EBPβ and MyD88.  In addition, in mouse models of intracellular infection of T. gondii and M. tuberculosis, specific elimination of Arg1 in mice macrophage favor host survival and clearance of pathogensl.

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3.      El Kasmi, K.C., et al. Toll-like receptor-induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens. Nat. Immunol. 9, 1399-1406 (2008).

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