Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease

被引：190

作者：

Pillai, Padmini S. ^{[1
]}

Molony, Ryan D. ^{[1
]}

Martinod, Kimberly ^{[2
]}

Dong, Huiping ^{[1
]}

Pang, Iris K. ^{[1
]}

Tal, Michal C. ^{[1
,9
]}

Solis, Angel G. ^{[1
]}

Bielecki, Piotr ^{[1
]}

Mohanty, Subhasis ^{[3
]}

Trentalange, Mark ^{[4
]}

Homer, Robert J. ^{[5
]}

Flavell, Richard A. ^{[1
,8
]}

Wagner, Denisa D. ^{[2
]}

Montgomery, Ruth R. ^{[6
]}

Shaw, Albert C. ^{[3
]}

Staeheli, Peter ^{[7
]}

Iwasaki, Akiko ^{[1
,8
]}

机构：

[1] Yale Univ, Sch Med, Dept Immunobiol, 333 Cedar St, New Haven, CT 06520 USA

[2] Harvard Univ, Boston Childrens Hosp, Sch Med, Program Cellular & Mol Med, Boston, MA USA

[3] Yale Univ, Sch Med, Dept Internal Med, Sect Infect Dis, 333 Cedar St, New Haven, CT 06520 USA

[4] Yale Univ, Sch Med, Dept Internal Med, 333 Cedar St, New Haven, CT 06520 USA

[5] Yale Univ, Sch Med, Dept Pathol, 333 Cedar St, New Haven, CT 06520 USA

[6] Yale Univ, Sch Med, Dept Internal Med, Sect Rheumatol, 333 Cedar St, New Haven, CT 06520 USA

[7] Univ Med Ctr Freiburg, Inst Virol, Inst Med Mikrobiol & Hyg, Hermann Herder Str 11, D-79104 Freiburg, Germany

[8] Yale Univ, Sch Med, Howard Hughes Med Inst, 333 Cedar St, New Haven, CT 06520 USA

[9] Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA

来源：

SCIENCE | 2016年 / 352卷 / 6284期

关键词：

A-VIRUS-INFECTION; DENDRITIC CELLS; TOLERANCE; MICE; VACCINATION; RESPONSES; IMMUNITY; GENES; MOUSE;

D O I：

10.1126/science.aaf3926

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：

Influenza A virus (IAV) causes up to half a million deaths worldwide annually, 90% of which occur in older adults. We show that IAV-infected monocytes from older humans have impaired antiviral interferon production but retain intact inflammasome responses. To understand the in vivo consequence, we used mice expressing a functional Mx gene encoding a major interferon-induced effector against IAV in humans. In Mx1-intact mice with weakened resistance due to deficiencies in Mavs and Tlr7, we found an elevated respiratory bacterial burden. Notably, mortality in the absence of Mavs and Tlr7 was independent of viral load or MyD88-dependent signaling but dependent on bacterial burden, caspase-1/11, and neutrophil-dependent tissue damage. Therefore, in the context of weakened antiviral resistance, vulnerability to IAV disease is a function of caspase-dependent pathology.

引用

页码：463 / 466

页数：4

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