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PMID: 18978793 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

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

Nature immunology ·Vol. 9 ·No. 12 ·2008-12-00 ·Pages 1399-406

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 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.

MeSH Terms
Animals Arginase/immunology,metabolism Bacterial Infections/immunology CCAAT-Enhancer-Binding Protein-beta/immunology,metabolism Immunoblotting Immunohistochemistry Macrophages/immunology,microbiology Mice Mice, Knockout Myeloid Differentiation Factor 88/immunology,metabolism STAT6 Transcription Factor/immunology,metabolism Toll-Like Receptors/immunology,metabolism
Chemicals
CCAAT-Enhancer-Binding Protein-beta Myeloid Differentiation Factor 88 STAT6 Transcription Factor Toll-Like Receptors Arginase
Authors & Affiliations
18 authors, click to expand affiliations / ORCID
El Kasmi Karim C
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38015, USA.
Qualls Joseph E
Pesce John T
Smith Amber M
Thompson Robert W
Henao-Tamayo Marcela
Basaraba Randall J
König 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
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.1671
Published
2008-12-00
Epub
2008-00-02
Pages
1399-406
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC2584974
Subset
IM
Grants
NIAID NIH HHS · R01 AI066046 · United States
NIAID NIH HHS · AI062921 · United States
NCI NIH HHS · P30 CA021765-30 · United States
NIAID NIH HHS · AI27913 · United States
Intramural NIH HHS · United States
NCI NIH HHS · P30 CA21765 · United States
NIAID NIH HHS · R01 AI062921-04 · United States
NCI NIH HHS · P30 CA021765 · United States
NIAID NIH HHS · R01 AI062921 · United States
NIAID NIH HHS · AI66046 · United States
NIAID NIH HHS · R01 AI027913 · United States
External Links
PubMed source DOI: 10.1038/ni.1671 PMC Full Text View journal details
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