B and T Lymphocyte Attenuator Tempers Early Infection Immunity

被引：47

作者：

Sun, Yonglian ^{[1
]}

Brown, Nicholas K. ^{[1
]}

Ruddy, Matthew J. ^{[1
]}

Miller, Mendy L. ^{[1
]}

Lee, Youjin ^{[1
]}

Wang, Yang ^{[1
]}

Murphy, Kenneth M. ^{[2
,3
]}

Pfeffer, Klaus ^{[4
]}

Chen, Lieping ^{[5
]}

Kaye, Jonathan ^{[6
]}

Fu, Yang-Xin ^{[1
]}

机构：

[1] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA

[2] Washington Univ, Dept Pathol, St Louis, MO 63110 USA

[3] Washington Univ, Ctr Immunol, St Louis, MO 63110 USA

[4] Univ Dusseldorf, Inst Med Microbiol, Dusseldorf, Germany

[5] Johns Hopkins Univ, Dept Dermatol, Baltimore, MD 21205 USA

[6] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA

来源：

JOURNAL OF IMMUNOLOGY | 2009年 / 183卷 / 03期

基金：

美国国家卫生研究院;

关键词：

HERPESVIRUS ENTRY MEDIATOR; LYMPHOTOXIN BETA-RECEPTOR; LISTERIA-MONOCYTOGENES; TNF SUPERFAMILY; CELL-SURVIVAL; LIGHT; HOMEOSTASIS; ACTIVATION; RESPONSES; PATHWAY;

D O I：

10.4049/jimmunol.0801866

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Coinhibitory pathways are thought to act in later stages of an adaptive immune response, but whether coinhibition contributes to early innate immunity is unclear. We show that engagement of the newly discovered coinhibitory receptor B and T lymphocyte attenuator (BTLA) by herpesvirus entry mediator (HVEM) is critical for negatively regulating early host immunity against intracellular bacteria. Both HVEM-/- and BTLA(-/-), but not LIGHT(-/-), mice are more resistant to listeriosis compared with wild-type mice, and blockade of the BTLA pathway promotes, while engagement inhibits, early bacterial clearance. Differences in bacterial clearance were seen as early as 1 day postinfection, implicating the initial innate response. Therefore, innate cell function in BTLA(-/-) mice was studied. We show that innate cells from BTLA(-/-) mice secrete significantly more proinflammatory cytokines upon stimulation with heat-killed Listeria. These results provide the first evidence that a coinhibitory pathway plays a critical role in regulating early host innate immunity against infection. The Journal of Immunology, 2009, 183: 1946-1951.

引用

页码：1946 / 1951

页数：6

共 32 条

[1] NATURAL IMMUNITY - A T-CELL-INDEPENDENT PATHWAY OF MACROPHAGE ACTIVATION, DEFINED IN THE SCID MOUSE [J].