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

被引：500

作者：

El Kasmi, Karim C. ^{[1
,8
]}

Qualls, Joseph E. ^{[1
,8
]}

Pesce, John T. ^{[2
]}

Smith, Amber M. ^{[1
,8
]}

Thompson, Robert W. ^{[2
]}

Henao-Tamayo, Marcela ^{[3
]}

Basaraba, Randall J. ^{[3
]}

Koenig, Till ^{[4
,5
]}

Schleicher, Ulrike

Koo, Mi-Sun ^{[6
]}

Kaplan, Gilla ^{[6
]}

Fitzgerald, Katherine A. ^{[7
]}

Tuomanen, Elaine I.

Orme, Ian M. ^{[3
]}

Kanneganti, Thirumala-Devi ^{[1
]}

Bogdan, Christian

Wynn, Thomas A. ^{[2
]}

Murray, Peter J. ^{[1
,8
]}

机构：

[1] St Jude Childrens Hosp, Dept Immunol, Memphis, TN 38015 USA

[2] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA

[3] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA

[4] Univ Clin Freiburg, Inst Med Microbiol & Hyg, Dept Microbiol & Hyg, D-79104 Freiburg, Germany

[5] Univ Clin Erlangen, Inst Clin Microbiol Immunol & Hyg, D-91054 Erlangen, Germany

[6] Univ Med & Dent New Jersey, Publ Hlth Res Inst Ctr, Lab Mycobacterial Immun & Pathogenesis, Newark, NJ 07103 USA

[7] Univ Massachusetts, Sch Med, Dept Immunol & Infect Dis, Worcester, MA 01605 USA

[8] St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38015 USA

来源：

NATURE IMMUNOLOGY | 2008年 / 9卷 / 12期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/ni.1671

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：1399 / 1406

页数：8

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