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

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.

Pubmed ID: 18978793


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


Nature immunology

Publication Data

December 14, 2008

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI062921
  • Agency: NIAID NIH HHS, Id: AI27913
  • Agency: NIAID NIH HHS, Id: AI66046
  • Agency: NCI NIH HHS, Id: P30 CA021765
  • Agency: NCI NIH HHS, Id: P30 CA021765-30
  • Agency: NCI NIH HHS, Id: P30 CA21765
  • Agency: NIAID NIH HHS, Id: R01 AI062921
  • Agency: NIAID NIH HHS, Id: R01 AI062921-04
  • Agency: Intramural NIH HHS, Id:

Mesh Terms

  • 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