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

Virginia Castiglia; Alessandra Piersigilli; Florian Ebner; Marton Janos; Oliver Goldmann; Ursula Damböck; Andrea Kröger; Sigfried Weiss; Sylvia Knapp; Amanda M Jamieson; Carsten Kirschning; Ulrich Kalinke; Birgit Strobl; Mathias Müller; Dagmar Stoiber; Stefan Lienenklaus; Pavel Kovarik

doi:10.1016/j.chom.2016.02.003

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

Virginia Castiglia, Alessandra Piersigilli, Florian Ebner, Marton Janos, Oliver Goldmann, Ursula Damböck, Andrea Kröger, Sigfried Weiss, Sylvia Knapp, Amanda M Jamieson, Carsten Kirschning, Ulrich Kalinke, Birgit Strobl, Mathias Müller, Dagmar Stoiber, Stefan Lienenklaus, Pavel Kovarik

Research output: Journal article (peer-reviewed) › Journal article

75 Citations (Scopus)

Abstract

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-1β. 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-β, which is significantly induced by S. pyogenes 23S rRNA in an Irf5-dependent manner. Our study establishes IL-1β and IFN-I levels as key homeostatic variables of protective, yet tuned, immune responses against severe invasive bacterial infection.

Original language	English
Pages (from-to)	375-387
Number of pages	13
Journal	Cell Host and Microbe
Volume	19
Issue number	3
DOIs	https://doi.org/10.1016/j.chom.2016.02.003
Publication status	Published - 09 Mar 2016
Externally published	Yes

Keywords

Animals
Disease Models, Animal
Interferon Type I/metabolism
Interleukin-1beta/metabolism
Mice
Mice, Knockout
Signal Transduction
Soft Tissue Infections/immunology
Streptococcal Infections/immunology
Survival Analysis

Access to Document

10.1016/j.chom.2016.02.003

Cite this

Castiglia, V., Piersigilli, A., Ebner, F., Janos, M., Goldmann, O., Damböck, U., Kröger, A., Weiss, S., Knapp, S., Jamieson, A. M., Kirschning, C., Kalinke, U., Strobl, B., Müller, M., Stoiber, D., Lienenklaus, S., & Kovarik, P. (2016). Type I Interferon Signaling Prevents IL-1β-Driven Lethal Systemic Hyperinflammation during Invasive Bacterial Infection of Soft Tissue. Cell Host and Microbe, 19(3), 375-387. https://doi.org/10.1016/j.chom.2016.02.003

@article{b4cc6c0922d24cad99f9664d3e1393ae,

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

abstract = "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-1β. 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-β, which is significantly induced by S. pyogenes 23S rRNA in an Irf5-dependent manner. Our study establishes IL-1β and IFN-I levels as key homeostatic variables of protective, yet tuned, immune responses against severe invasive bacterial infection.",

keywords = "Animals, Disease Models, Animal, Interferon Type I/metabolism, Interleukin-1beta/metabolism, Mice, Mice, Knockout, Signal Transduction, Soft Tissue Infections/immunology, Streptococcal Infections/immunology, Survival Analysis",

author = "Virginia Castiglia and Alessandra Piersigilli and Florian Ebner and Marton Janos and Oliver Goldmann and Ursula Damb{\"o}ck and Andrea Kr{\"o}ger and Sigfried Weiss and Sylvia Knapp and Jamieson, {Amanda M} and Carsten Kirschning and Ulrich Kalinke and Birgit Strobl and Mathias M{\"u}ller and Dagmar Stoiber and Stefan Lienenklaus and Pavel Kovarik",

note = "Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

month = mar,

day = "9",

doi = "10.1016/j.chom.2016.02.003",

language = "English",

volume = "19",

pages = "375--387",

journal = "Cell Host and Microbe",

issn = "1931-3128",

publisher = "Cell Press",

number = "3",

}

Castiglia, V, Piersigilli, A, Ebner, F, Janos, M, Goldmann, O, Damböck, U, Kröger, A, Weiss, S, Knapp, S, Jamieson, AM, Kirschning, C, Kalinke, U, Strobl, B, Müller, M, Stoiber, D, Lienenklaus, S & Kovarik, P 2016, 'Type I Interferon Signaling Prevents IL-1β-Driven Lethal Systemic Hyperinflammation during Invasive Bacterial Infection of Soft Tissue', Cell Host and Microbe, vol. 19, no. 3, pp. 375-387. https://doi.org/10.1016/j.chom.2016.02.003

TY - JOUR

T1 - Type I Interferon Signaling Prevents IL-1β-Driven Lethal Systemic Hyperinflammation during Invasive Bacterial Infection of Soft Tissue

AU - Castiglia, Virginia

AU - Piersigilli, Alessandra

AU - Ebner, Florian

AU - Janos, Marton

AU - Goldmann, Oliver

AU - Damböck, Ursula

AU - Kröger, Andrea

AU - Weiss, Sigfried

AU - Knapp, Sylvia

AU - Jamieson, Amanda M

AU - Kirschning, Carsten

AU - Kalinke, Ulrich

AU - Strobl, Birgit

AU - Müller, Mathias

AU - Stoiber, Dagmar

AU - Lienenklaus, Stefan

AU - Kovarik, Pavel

PY - 2016/3/9

Y1 - 2016/3/9

N2 - 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-1β. 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-β, which is significantly induced by S. pyogenes 23S rRNA in an Irf5-dependent manner. Our study establishes IL-1β and IFN-I levels as key homeostatic variables of protective, yet tuned, immune responses against severe invasive bacterial infection.

AB - 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-1β. 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-β, which is significantly induced by S. pyogenes 23S rRNA in an Irf5-dependent manner. Our study establishes IL-1β and IFN-I levels as key homeostatic variables of protective, yet tuned, immune responses against severe invasive bacterial infection.

KW - Animals

KW - Disease Models, Animal

KW - Interferon Type I/metabolism

KW - Interleukin-1beta/metabolism

KW - Mice

KW - Mice, Knockout

KW - Signal Transduction

KW - Soft Tissue Infections/immunology

KW - Streptococcal Infections/immunology

KW - Survival Analysis

UR - http://www.scopus.com/inward/record.url?scp=84961784283&partnerID=8YFLogxK

U2 - 10.1016/j.chom.2016.02.003

DO - 10.1016/j.chom.2016.02.003

M3 - Journal article

C2 - 26962946

SN - 1931-3128

VL - 19

SP - 375

EP - 387

JO - Cell Host and Microbe

JF - Cell Host and Microbe

IS - 3

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this