Blockade of Chronic Type I Interferon Signaling to Control Persistent LCMV Infection

被引：556

作者：

Wilson, Elizabeth B. ^{[1
,2
]}

Yamada, Douglas H. ^{[1
,2
]}

Elsaesser, Heidi ^{[1
,2
]}

Herskovitz, Jonathan ^{[1
,2
]}

Deng, Jane ^{[3
]}

Cheng, Genhong ^{[1
,2
]}

Aronow, Bruce J. ^{[4
,5
,6
]}

Karp, Christopher L. ^{[6
,7
]}

Brooks, David G. ^{[1
,2
]}

机构：

[1] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, David Geffen Sch Med, UCLA AIDS Inst, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA

[4] Cincinnati Childrens Hosp Res Fdn, Div Biomed Informat, Cincinnati, OH 45267 USA

[5] Cincinnati Childrens Hosp Res Fdn, Div Dev Biol, Cincinnati, OH 45267 USA

[6] Univ Cincinnati, Coll Med, Cincinnati, OH 45267 USA

[7] Cincinnati Childrens Hosp Res Fdn, Div Mol Immunol, Cincinnati, OH 45267 USA

来源：

SCIENCE | 2013年 / 340卷 / 6129期

关键词：

CHRONIC HEPATITIS-C; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; CHRONIC VIRAL-INFECTION; T-CELLS; INTERLEUKIN-10; RECEPTOR; EXPRESSION; IL-10; GAMMA; PROGRESSION;

D O I：

10.1126/science.1235208

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Type I interferons (IFN-I) are critical for antiviral immunity; however, chronic IFN-I signaling is associated with hyperimmune activation and disease progression in persistent infections. We demonstrated in mice that blockade of IFN-I signaling diminished chronic immune activation and immune suppression, restored lymphoid tissue architecture, and increased immune parameters associated with control of virus replication, ultimately facilitating clearance of the persistent infection. The accelerated control of persistent infection induced by blocking IFN-I signaling required CD4 T cells and was associated with enhanced IFN-gamma production. Thus, we demonstrated that interfering with chronic IFN-I signaling during persistent infection redirects the immune environment to enable control of infection.

引用

页码：202 / 207

页数：7

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