Type I interferon contributes to noncanonical inflammasome activation, mediates immunopathology, and impairs protective immunity during fatal infection with lipopolysaccharide-negative ehrlichiae.
Identifieur interne : 000246 ( Main/Exploration ); précédent : 000245; suivant : 000247Type I interferon contributes to noncanonical inflammasome activation, mediates immunopathology, and impairs protective immunity during fatal infection with lipopolysaccharide-negative ehrlichiae.
Auteurs : Qin Yang [États-Unis] ; Heather L. Stevenson [États-Unis] ; Melanie J. Scott [États-Unis] ; Nahed Ismail [États-Unis]Source :
- The American journal of pathology [ 1525-2191 ] ; 2015.
Descripteurs français
- KwdFr :
- Animaux, Caspases (génétique), Caspases (immunologie), Ehrlichia (immunologie), Ehrlichiose (anatomopathologie), Ehrlichiose (génétique), Ehrlichiose (immunologie), Immunité cellulaire, Inflammasomes (immunologie), Interféron de type I (génétique), Interféron de type I (immunologie), Interféron gamma (génétique), Interféron gamma (immunologie), Interleukine-1 alpha (génétique), Interleukine-1 bêta (immunologie), Interleukine-10 (génétique), Interleukine-10 (immunologie), Lipopolysaccharides, Lymphocytes auxiliaires Th1 (anatomopathologie), Lymphocytes auxiliaires Th1 (immunologie), Récepteur à l'interféron alpha-bêta (génétique), Récepteur à l'interféron alpha-bêta (immunologie), Souris, Souris knockout, Transduction du signal (génétique), Transduction du signal (immunologie).
- MESH :
- anatomopathologie : Ehrlichiose, Lymphocytes auxiliaires Th1.
- génétique : Caspases, Ehrlichiose, Interféron de type I, Interféron gamma, Interleukine-1 alpha, Interleukine-10, Récepteur à l'interféron alpha-bêta, Transduction du signal.
- immunologie : Caspases, Ehrlichia, Ehrlichiose, Inflammasomes, Interféron de type I, Interféron gamma, Interleukine-1 bêta, Interleukine-10, Lymphocytes auxiliaires Th1, Récepteur à l'interféron alpha-bêta, Transduction du signal.
- Animaux, Immunité cellulaire, Lipopolysaccharides, Souris, Souris knockout.
English descriptors
- KwdEn :
- Animals, Caspases (genetics), Caspases (immunology), Ehrlichia (immunology), Ehrlichiosis (genetics), Ehrlichiosis (immunology), Ehrlichiosis (pathology), Immunity, Cellular, Inflammasomes (immunology), Interferon Type I (genetics), Interferon Type I (immunology), Interferon-gamma (genetics), Interferon-gamma (immunology), Interleukin-10 (genetics), Interleukin-10 (immunology), Interleukin-1alpha (genetics), Interleukin-1beta (immunology), Lipopolysaccharides, Mice, Mice, Knockout, Receptor, Interferon alpha-beta (genetics), Receptor, Interferon alpha-beta (immunology), Signal Transduction (genetics), Signal Transduction (immunology), Th1 Cells (immunology), Th1 Cells (pathology).
- MESH :
- chemical , genetics : Caspases, Interferon Type I, Interferon-gamma, Interleukin-10, Interleukin-1alpha, Receptor, Interferon alpha-beta.
- chemical , immunology : Caspases, Inflammasomes, Interferon Type I, Interferon-gamma, Interleukin-10, Interleukin-1beta, Receptor, Interferon alpha-beta.
- genetics : Ehrlichiosis, Signal Transduction.
- immunology : Ehrlichia, Ehrlichiosis, Signal Transduction, Th1 Cells.
- pathology : Ehrlichiosis, Th1 Cells.
- Animals, Immunity, Cellular, Lipopolysaccharides, Mice, Mice, Knockout.
Abstract
Ehrlichia species are intracellular bacteria that cause fatal ehrlichiosis, mimicking toxic shock syndrome in humans and mice. Virulent ehrlichiae induce inflammasome activation leading to caspase-1 cleavage and IL-18 secretion, which contribute to development of fatal ehrlichiosis. We show that fatal infection triggers expression of inflammasome components, activates caspase-1 and caspase-11, and induces host-cell death and secretion of IL-1β, IL-1α, and type I interferon (IFN-I). Wild-type and Casp1(-/-) mice were highly susceptible to fatal ehrlichiosis, had overwhelming infection, and developed extensive tissue injury. Nlrp3(-/-) mice effectively cleared ehrlichiae, but displayed acute mortality and developed liver injury similar to wild-type mice. By contrast, Ifnar1(-/-) mice were highly resistant to fatal disease and had lower bacterial burden, attenuated pathology, and prolonged survival. Ifnar1(-/-) mice also had improved protective immune responses mediated by IFN-γ and CD4(+) Th1 and natural killer T cells, with lower IL-10 secretion by T cells. Importantly, heightened resistance of Ifnar1(-/-) mice correlated with improved autophagosome processing, and attenuated noncanonical inflammasome activation indicated by decreased activation of caspase-11 and decreased IL-1β, compared with other groups. Our findings demonstrate that IFN-I signaling promotes host susceptibility to fatal ehrlichiosis, because it mediates ehrlichia-induced immunopathology and supports bacterial replication, perhaps via activation of noncanonical inflammasomes, reduced autophagy, and suppression of protective CD4(+) T cells and natural killer T-cell responses against ehrlichiae.
DOI: 10.1016/j.ajpath.2014.10.005
PubMed: 25481711
Affiliations:
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Le document en format XML
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Electronic address: ismailn@upmc.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh</wicri:cityArea></affiliation></author></analytic><series><title level="j">The American journal of pathology</title><idno type="eISSN">1525-2191</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Caspases (genetics)</term><term>Caspases (immunology)</term><term>Ehrlichia (immunology)</term><term>Ehrlichiosis (genetics)</term><term>Ehrlichiosis (immunology)</term><term>Ehrlichiosis (pathology)</term><term>Immunity, Cellular</term><term>Inflammasomes (immunology)</term><term>Interferon Type I (genetics)</term><term>Interferon Type I (immunology)</term><term>Interferon-gamma (genetics)</term><term>Interferon-gamma (immunology)</term><term>Interleukin-10 (genetics)</term><term>Interleukin-10 (immunology)</term><term>Interleukin-1alpha (genetics)</term><term>Interleukin-1beta (immunology)</term><term>Lipopolysaccharides</term><term>Mice</term><term>Mice, Knockout</term><term>Receptor, Interferon alpha-beta (genetics)</term><term>Receptor, Interferon alpha-beta (immunology)</term><term>Signal Transduction (genetics)</term><term>Signal Transduction (immunology)</term><term>Th1 Cells (immunology)</term><term>Th1 Cells (pathology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Caspases (génétique)</term><term>Caspases (immunologie)</term><term>Ehrlichia (immunologie)</term><term>Ehrlichiose (anatomopathologie)</term><term>Ehrlichiose (génétique)</term><term>Ehrlichiose (immunologie)</term><term>Immunité cellulaire</term><term>Inflammasomes (immunologie)</term><term>Interféron de type I (génétique)</term><term>Interféron de type I (immunologie)</term><term>Interféron gamma (génétique)</term><term>Interféron gamma (immunologie)</term><term>Interleukine-1 alpha (génétique)</term><term>Interleukine-1 bêta (immunologie)</term><term>Interleukine-10 (génétique)</term><term>Interleukine-10 (immunologie)</term><term>Lipopolysaccharides</term><term>Lymphocytes auxiliaires Th1 (anatomopathologie)</term><term>Lymphocytes auxiliaires Th1 (immunologie)</term><term>Récepteur à l'interféron alpha-bêta (génétique)</term><term>Récepteur à l'interféron alpha-bêta (immunologie)</term><term>Souris</term><term>Souris knockout</term><term>Transduction du signal (génétique)</term><term>Transduction du signal (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Caspases</term><term>Interferon Type I</term><term>Interferon-gamma</term><term>Interleukin-10</term><term>Interleukin-1alpha</term><term>Receptor, Interferon alpha-beta</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Caspases</term><term>Inflammasomes</term><term>Interferon Type I</term><term>Interferon-gamma</term><term>Interleukin-10</term><term>Interleukin-1beta</term><term>Receptor, Interferon alpha-beta</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Ehrlichiose</term><term>Lymphocytes auxiliaires Th1</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Ehrlichiosis</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Caspases</term><term>Ehrlichiose</term><term>Interféron de type I</term><term>Interféron gamma</term><term>Interleukine-1 alpha</term><term>Interleukine-10</term><term>Récepteur à l'interféron alpha-bêta</term><term>Transduction du signal</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Caspases</term><term>Ehrlichia</term><term>Ehrlichiose</term><term>Inflammasomes</term><term>Interféron de type I</term><term>Interféron gamma</term><term>Interleukine-1 bêta</term><term>Interleukine-10</term><term>Lymphocytes auxiliaires Th1</term><term>Récepteur à l'interféron alpha-bêta</term><term>Transduction du signal</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Ehrlichia</term><term>Ehrlichiosis</term><term>Signal Transduction</term><term>Th1 Cells</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Ehrlichiosis</term><term>Th1 Cells</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Immunity, Cellular</term><term>Lipopolysaccharides</term><term>Mice</term><term>Mice, Knockout</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Immunité cellulaire</term><term>Lipopolysaccharides</term><term>Souris</term><term>Souris knockout</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Ehrlichia species are intracellular bacteria that cause fatal ehrlichiosis, mimicking toxic shock syndrome in humans and mice. Virulent ehrlichiae induce inflammasome activation leading to caspase-1 cleavage and IL-18 secretion, which contribute to development of fatal ehrlichiosis. We show that fatal infection triggers expression of inflammasome components, activates caspase-1 and caspase-11, and induces host-cell death and secretion of IL-1β, IL-1α, and type I interferon (IFN-I). Wild-type and Casp1(-/-) mice were highly susceptible to fatal ehrlichiosis, had overwhelming infection, and developed extensive tissue injury. Nlrp3(-/-) mice effectively cleared ehrlichiae, but displayed acute mortality and developed liver injury similar to wild-type mice. By contrast, Ifnar1(-/-) mice were highly resistant to fatal disease and had lower bacterial burden, attenuated pathology, and prolonged survival. Ifnar1(-/-) mice also had improved protective immune responses mediated by IFN-γ and CD4(+) Th1 and natural killer T cells, with lower IL-10 secretion by T cells. Importantly, heightened resistance of Ifnar1(-/-) mice correlated with improved autophagosome processing, and attenuated noncanonical inflammasome activation indicated by decreased activation of caspase-11 and decreased IL-1β, compared with other groups. Our findings demonstrate that IFN-I signaling promotes host susceptibility to fatal ehrlichiosis, because it mediates ehrlichia-induced immunopathology and supports bacterial replication, perhaps via activation of noncanonical inflammasomes, reduced autophagy, and suppression of protective CD4(+) T cells and natural killer T-cell responses against ehrlichiae.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Pennsylvanie</li></region></list><tree><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Yang, Qin" sort="Yang, Qin" uniqKey="Yang Q" first="Qin" last="Yang">Qin Yang</name></region><name sortKey="Ismail, Nahed" sort="Ismail, Nahed" uniqKey="Ismail N" first="Nahed" last="Ismail">Nahed Ismail</name><name sortKey="Scott, Melanie J" sort="Scott, Melanie J" uniqKey="Scott M" first="Melanie J" last="Scott">Melanie J. Scott</name><name sortKey="Stevenson, Heather L" sort="Stevenson, Heather L" uniqKey="Stevenson H" first="Heather L" last="Stevenson">Heather L. Stevenson</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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