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

共 50 条

[1] Macrophage arginase regulation by CCAAT/enhancer-binding protein β
Albina, JE
Mahoney, EJ
Daley, JM
Wesche, DE
Morris, SM
Reichner, JS
[J]. SHOCK, 2005, 23 (02): : 168 - 172
[2] Protective immune mechanisms in helminth infection
Anthony, Robert M.
Rutitzky, Laura I.
Urban, Joseph F., Jr.
Stadecker, Miguel J.
Gause, William C.
[J]. NATURE REVIEWS IMMUNOLOGY, 2007, 7 (12) : 975 - 987
[3] Nitric oxide and the immune response
Bogdan, C
[J]. NATURE IMMUNOLOGY, 2001, 2 (10) : 907 - 916
[4] Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors
Brightbill, HD
Libraty, DH
Krutzik, SR
Yang, RB
Belisle, JT
Bleharski, JR
Maitland, M
Norgard, MV
Plevy, SE
Smale, ST
Brennan, PJ
Bloom, BR
Godowski, PJ
Modlin, RL
[J]. SCIENCE, 1999, 285 (5428) : 732 - 736
[5] Regulation of immune responses by L- arginine metabolism
Bronte, V
Zanovello, P
[J]. NATURE REVIEWS IMMUNOLOGY, 2005, 5 (08) : 641 - 654
[6] Spermine causes loss of innate immune response to Helicobacter pylori by inhibition of inducible nitric-oxide synthase translation
Bussière, FI
Chaturvedi, R
Cheng, YL
Gobert, AP
Asim, M
Blumberg, DR
Xu, HX
Kim, PY
Hacker, A
Casero, RA
Wilson, KT
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (04) : 2409 - 2412
[7] KILLING OF VIRULENT MYCOBACTERIUM-TUBERCULOSIS BY REACTIVE NITROGEN INTERMEDIATES PRODUCED BY ACTIVATED MURINE MACROPHAGES
CHAN, J
XING, Y
MAGLIOZZO, RS
BLOOM, BR
[J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1992, 175 (04) : 1111 - 1122
[8] Analysis of nitric oxide synthase and nitrotyrosine expression in human pulmonary tuberculosis
Choi, HS
Rai, PR
Chu, HW
Cool, C
Chan, ED
[J]. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2002, 166 (02) : 178 - 186
[9] Expression of the nitric oxide synthase 2 gene is not essential for early control of Mycobacterium tuberculosis in the murine lung
Cooper, AM
Pearl, JE
Brooks, JV
Ehlers, S
Orme, IM
[J]. INFECTION AND IMMUNITY, 2000, 68 (12) : 6879 - 6882
[10] Mechanism of inducible nitric oxide synthase exclusion from mycobacterial phagosomes
Davis, Alexander S.
Vergne, Isabelle
Master, Sharon S.
Kyei, George B.
Chua, Jennifer
Deretic, Vojo
[J]. PLOS PATHOGENS, 2007, 3 (12) : 1887 - 1894

← 1 2 3 4 5 →