Type I Interferon Signaling Prevents IL-1β-Driven Lethal Systemic Hyperinflammation during Invasive Bacterial Infection of Soft Tissue

被引：77

作者：

Castiglia, Virginia ^{[1
]}

Piersigilli, Alessandra ^{[2
,3
]}

Ebner, Florian ^{[1
]}

Janos, Marton ^{[1
]}

Goldmann, Oliver ^{[4
]}

Damboeck, Ursula ^{[1
]}

Kroeger, Andrea ^{[5
,6
]}

Weiss, Sigfried ^{[6
]}

Knapp, Sylvia ^{[7
,8
]}

Jamieson, Amanda M. ^{[9
]}

Kirschning, Carsten ^{[10
]}

Kalinke, Ulrich ^{[11
,12
]}

Strobl, Birgit ^{[13
]}

Mueller, Mathias ^{[13
]}

Stoiber, Dagmar ^{[14
,15
]}

Lienenklaus, Stefan ^{[11
,12
,16
]}

Kovarik, Pavel ^{[1
]}

机构：

[1] Univ Vienna, Max F Perutz Labs, Vienna Bioctr VBC, A-1030 Vienna, Austria

[2] Univ Bern, Inst Anim Pathol COMPATH, CH-3012 Bern, Switzerland

[3] Ecole Polytech Fed Lausanne, Fac Life Sci, CH-1015 Lausanne, Switzerland

[4] Helmholtz Ctr Infect Res, Infect Immunol Res Grp, D-38124 Braunschweig, Germany

[5] Univ Magdeburg, Inst Med Microbiol, D-39106 Magdeburg, Germany

[6] Helmholtz Ctr Infect Res, Dept Mol Immunol, D-38124 Braunschweig, Germany

[7] Austrian Acad Sci, Ctr Mol Med, A-1090 Vienna, Austria

[8] Med Univ Vienna, Dept Med 1, Lab Infect Biol, A-1090 Vienna, Austria

[9] Brown Univ, Div Biol & Med, Dept Mol Microbiol & Immunol, Providence, RI 02912 USA

[10] Univ Duisburg Essen, Inst Med Microbiol, D-45147 Essen, Germany

[11] Hannover Med Sch, Ctr Expt & Clin Infect Res, TWINCORE, Inst Expt Infect Res, D-30625 Hannover, Germany

[12] Helmholtz Ctr Infect Res, D-30625 Hannover, Germany

[13] Univ Vet Med Vienna, Inst Anim Breeding & Genet, A-1210 Vienna, Austria

[14] Med Univ Vienna, Inst Pharmacol, A-1090 Vienna, Austria

[15] Ludwig Boltzmann Inst Canc Res, A-1090 Vienna, Austria

[16] Hannover Med Sch, Inst Lab Anim Sci, D-30625 Hannover, Germany

来源：

CELL HOST & MICROBE | 2016年 / 19卷 / 03期

基金：

奥地利科学基金会;

关键词：

GROUP-A-STREPTOCOCCUS; INFLAMMATORY RESPONSE; DENDRITIC CELLS; IFN-GAMMA; MACROPHAGES; RNA; INNATE; MICE; RECOGNITION; RESISTANCE;

D O I：

10.1016/j.chom.2016.02.003

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Type I interferons (IFN-Is) are fundamental for antiviral immunity, but their role in bacterial infections is contradictory and incompletely described. Streptococcus pyogenes activates IFN-I production in innate immune cells, and IFN-I receptor 1 (Ifnar1)-deficient mice are highly susceptible to S. pyogenes infection. Here we report that IFN-I signaling protects the host against invasive S. pyogenes infection by restricting inflammation-driven damage in distant tissues. Lethality following infection in Ifnar1-deficient mice is caused by systemically exacerbated levels of the proinflammatory cytokine IL-1 beta. Critical cellular effectors of IFN-I in vivo are LysM+ and CD11c+ myeloid cells, which exhibit suppression of Il1b transcription upon Ifnar1 engagement. These cells are also the major source of IFN-beta, which is significantly induced by S. pyogenes 23S rRNA in an Irf5-dependent manner. Our study establishes IL-1 beta and IFN-I levels as key homeostatic variables of protective, yet tuned, immune responses against severe invasive bacterial infection.

引用

页码：375 / 387

页数：13

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