RapamycinFungusV1, Main, Exploration, bibRecord, 000793

MyD88-dependent inflammasome activation and autophagy inhibition contributes to Ehrlichia-induced liver injury and toxic shock.

Identifieur interne : 000793 ( Main/Exploration ); précédent : 000792; suivant : 000794

MyD88-dependent inflammasome activation and autophagy inhibition contributes to Ehrlichia-induced liver injury and toxic shock.

Auteurs : Muhamuda Kader [États-Unis] ; Mounia Alaoui-El-Azher [États-Unis] ; Jennie Vorhauer [États-Unis] ; Bhushan B. Kode [États-Unis] ; Jakob Z. Wells [États-Unis] ; Donna Stolz [États-Unis] ; George Michalopoulos [États-Unis] ; Alan Wells [États-Unis] ; Melanie Scott [États-Unis] ; Nahed Ismail [États-Unis]

Source :

PLoS pathogens [ 1553-7374 ] ; 2017.

RBID : pubmed:29049365

Descripteurs français

English descriptors

Abstract

Severe hepatic inflammation is a common cause of acute liver injury following systemic infection with Ehrlichia, obligate Gram-negative intracellular bacteria that lack lipopolysaccharide (LPS). We have previously shown that type I IFN (IFN-I) and inflammasome activation are key host-pathogenic mediators that promote excessive inflammation and liver damage following fatal Ehrlichia infection. However, the underlying signals and mechanisms that regulate protective immunity and immunopathology during Ehrlichia infection are not well understood. To address this issue, we compared susceptibility to lethal Ixodes ovatus Ehrlichia (IOE) infection between wild type (WT) and MyD88-deficient (MyD88-/-) mice. We show here that MyD88-/- mice exhibited decreased inflammasome activation, attenuated liver injury, and were more resistant to lethal infection than WT mice, despite suppressed protective immunity and increased bacterial burden in the liver. MyD88-dependent inflammasome activation was also dependent on activation of the metabolic checkpoint kinase mammalian target of rapamycin complex 1 (mTORC1), inhibition of autophagic flux, and defective mitophagy in macrophages. Blocking mTORC1 signaling in infected WT mice and primary macrophages enhanced bacterial replication and attenuated inflammasome activation, suggesting autophagy promotes bacterial replication while inhibiting inflammasome activation. Finally, our data suggest TLR9 and IFN-I are upstream signaling mechanisms triggering MyD88-mediated mTORC1 and inflammasome activation in macrophages following Ehrlichia infection. This study reveals that Ehrlichia-induced liver injury and toxic shock are mediated by MyD88-dependent inflammasome activation and autophagy inhibition.

DOI: 10.1371/journal.ppat.1006644
PubMed: 29049365
PubMed Central: PMC5663626

Affiliations:

Links toward previous steps (curation, corpus...)

to stream Main, to step Corpus: 000699
to stream Main, to step Curation: 000699

Le document en format XML

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<author><name sortKey="Stolz, Donna" sort="Stolz, Donna" uniqKey="Stolz D" first="Donna" last="Stolz">Donna Stolz</name>
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<author><name sortKey="Michalopoulos, George" sort="Michalopoulos, George" uniqKey="Michalopoulos G" first="George" last="Michalopoulos">George Michalopoulos</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania</wicri:regionArea>
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<author><name sortKey="Wells, Alan" sort="Wells, Alan" uniqKey="Wells A" first="Alan" last="Wells">Alan Wells</name>
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<author><name sortKey="Scott, Melanie" sort="Scott, Melanie" uniqKey="Scott M" first="Melanie" last="Scott">Melanie Scott</name>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term>
<term>Autophagy (immunology)</term>
<term>Blotting, Western (MeSH)</term>
<term>Disease Models, Animal (MeSH)</term>
<term>Ehrlichia (immunology)</term>
<term>Ehrlichiosis (immunology)</term>
<term>Ehrlichiosis (metabolism)</term>
<term>Enzyme-Linked Immunosorbent Assay (MeSH)</term>
<term>Female (MeSH)</term>
<term>Flow Cytometry (MeSH)</term>
<term>Fluorescent Antibody Technique (MeSH)</term>
<term>Image Processing, Computer-Assisted (MeSH)</term>
<term>In Situ Nick-End Labeling (MeSH)</term>
<term>Inflammasomes (immunology)</term>
<term>Inflammasomes (metabolism)</term>
<term>Liver Failure, Acute (immunology)</term>
<term>Liver Failure, Acute (metabolism)</term>
<term>Liver Failure, Acute (microbiology)</term>
<term>Mice (MeSH)</term>
<term>Mice, Inbred C57BL (MeSH)</term>
<term>Mice, Knockout (MeSH)</term>
<term>Microscopy, Confocal (MeSH)</term>
<term>Microscopy, Electron, Transmission (MeSH)</term>
<term>Myeloid Differentiation Factor 88 (immunology)</term>
<term>Myeloid Differentiation Factor 88 (metabolism)</term>
<term>Real-Time Polymerase Chain Reaction (MeSH)</term>
<term>Shock, Septic (immunology)</term>
<term>Shock, Septic (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term>
<term>Autophagie (immunologie)</term>
<term>Choc septique (immunologie)</term>
<term>Choc septique (métabolisme)</term>
<term>Cytométrie en flux (MeSH)</term>
<term>Défaillance hépatique aigüe (immunologie)</term>
<term>Défaillance hépatique aigüe (microbiologie)</term>
<term>Défaillance hépatique aigüe (métabolisme)</term>
<term>Ehrlichia (immunologie)</term>
<term>Ehrlichiose (immunologie)</term>
<term>Ehrlichiose (métabolisme)</term>
<term>Facteur de différenciation myéloïde-88 (immunologie)</term>
<term>Facteur de différenciation myéloïde-88 (métabolisme)</term>
<term>Femelle (MeSH)</term>
<term>Inflammasomes (immunologie)</term>
<term>Inflammasomes (métabolisme)</term>
<term>Microscopie confocale (MeSH)</term>
<term>Microscopie électronique à transmission (MeSH)</term>
<term>Modèles animaux de maladie humaine (MeSH)</term>
<term>Méthode TUNEL (MeSH)</term>
<term>Réaction de polymérisation en chaine en temps réel (MeSH)</term>
<term>Souris (MeSH)</term>
<term>Souris de lignée C57BL (MeSH)</term>
<term>Souris knockout (MeSH)</term>
<term>Technique d'immunofluorescence (MeSH)</term>
<term>Technique de Western (MeSH)</term>
<term>Test ELISA (MeSH)</term>
<term>Traitement d'image par ordinateur (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Inflammasomes</term>
<term>Myeloid Differentiation Factor 88</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Autophagie</term>
<term>Choc septique</term>
<term>Défaillance hépatique aigüe</term>
<term>Ehrlichia</term>
<term>Ehrlichiose</term>
<term>Facteur de différenciation myéloïde-88</term>
<term>Inflammasomes</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Autophagy</term>
<term>Ehrlichia</term>
<term>Ehrlichiosis</term>
<term>Liver Failure, Acute</term>
<term>Shock, Septic</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Ehrlichiosis</term>
<term>Inflammasomes</term>
<term>Liver Failure, Acute</term>
<term>Myeloid Differentiation Factor 88</term>
<term>Shock, Septic</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiologie" xml:lang="fr"><term>Défaillance hépatique aigüe</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiology" xml:lang="en"><term>Liver Failure, Acute</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Choc septique</term>
<term>Défaillance hépatique aigüe</term>
<term>Ehrlichiose</term>
<term>Facteur de différenciation myéloïde-88</term>
<term>Inflammasomes</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Blotting, Western</term>
<term>Disease Models, Animal</term>
<term>Enzyme-Linked Immunosorbent Assay</term>
<term>Female</term>
<term>Flow Cytometry</term>
<term>Fluorescent Antibody Technique</term>
<term>Image Processing, Computer-Assisted</term>
<term>In Situ Nick-End Labeling</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Knockout</term>
<term>Microscopy, Confocal</term>
<term>Microscopy, Electron, Transmission</term>
<term>Real-Time Polymerase Chain Reaction</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Cytométrie en flux</term>
<term>Femelle</term>
<term>Microscopie confocale</term>
<term>Microscopie électronique à transmission</term>
<term>Modèles animaux de maladie humaine</term>
<term>Méthode TUNEL</term>
<term>Réaction de polymérisation en chaine en temps réel</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Souris knockout</term>
<term>Technique d'immunofluorescence</term>
<term>Technique de Western</term>
<term>Test ELISA</term>
<term>Traitement d'image par ordinateur</term>
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<front><div type="abstract" xml:lang="en">Severe hepatic inflammation is a common cause of acute liver injury following systemic infection with Ehrlichia, obligate Gram-negative intracellular bacteria that lack lipopolysaccharide (LPS). We have previously shown that type I IFN (IFN-I) and inflammasome activation are key host-pathogenic mediators that promote excessive inflammation and liver damage following fatal Ehrlichia infection. However, the underlying signals and mechanisms that regulate protective immunity and immunopathology during Ehrlichia infection are not well understood. To address this issue, we compared susceptibility to lethal Ixodes ovatus Ehrlichia (IOE) infection between wild type (WT) and MyD88-deficient (MyD88-/-) mice. We show here that MyD88-/- mice exhibited decreased inflammasome activation, attenuated liver injury, and were more resistant to lethal infection than WT mice, despite suppressed protective immunity and increased bacterial burden in the liver. MyD88-dependent inflammasome activation was also dependent on activation of the metabolic checkpoint kinase mammalian target of rapamycin complex 1 (mTORC1), inhibition of autophagic flux, and defective mitophagy in macrophages. Blocking mTORC1 signaling in infected WT mice and primary macrophages enhanced bacterial replication and attenuated inflammasome activation, suggesting autophagy promotes bacterial replication while inhibiting inflammasome activation. Finally, our data suggest TLR9 and IFN-I are upstream signaling mechanisms triggering MyD88-mediated mTORC1 and inflammasome activation in macrophages following Ehrlichia infection. This study reveals that Ehrlichia-induced liver injury and toxic shock are mediated by MyD88-dependent inflammasome activation and autophagy inhibition.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">29049365</PMID>
<DateCompleted><Year>2017</Year>
<Month>11</Month>
<Day>02</Day>
</DateCompleted>
<DateRevised><Year>2018</Year>
<Month>11</Month>
<Day>13</Day>
</DateRevised>
<Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">1553-7374</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>13</Volume>
<Issue>10</Issue>
<PubDate><Year>2017</Year>
<Month>Oct</Month>
</PubDate>
</JournalIssue>
<Title>PLoS pathogens</Title>
<ISOAbbreviation>PLoS Pathog</ISOAbbreviation>
</Journal>
<ArticleTitle>MyD88-dependent inflammasome activation and autophagy inhibition contributes to Ehrlichia-induced liver injury and toxic shock.</ArticleTitle>
<Pagination><MedlinePgn>e1006644</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.ppat.1006644</ELocationID>
<Abstract><AbstractText>Severe hepatic inflammation is a common cause of acute liver injury following systemic infection with Ehrlichia, obligate Gram-negative intracellular bacteria that lack lipopolysaccharide (LPS). We have previously shown that type I IFN (IFN-I) and inflammasome activation are key host-pathogenic mediators that promote excessive inflammation and liver damage following fatal Ehrlichia infection. However, the underlying signals and mechanisms that regulate protective immunity and immunopathology during Ehrlichia infection are not well understood. To address this issue, we compared susceptibility to lethal Ixodes ovatus Ehrlichia (IOE) infection between wild type (WT) and MyD88-deficient (MyD88-/-) mice. We show here that MyD88-/- mice exhibited decreased inflammasome activation, attenuated liver injury, and were more resistant to lethal infection than WT mice, despite suppressed protective immunity and increased bacterial burden in the liver. MyD88-dependent inflammasome activation was also dependent on activation of the metabolic checkpoint kinase mammalian target of rapamycin complex 1 (mTORC1), inhibition of autophagic flux, and defective mitophagy in macrophages. Blocking mTORC1 signaling in infected WT mice and primary macrophages enhanced bacterial replication and attenuated inflammasome activation, suggesting autophagy promotes bacterial replication while inhibiting inflammasome activation. Finally, our data suggest TLR9 and IFN-I are upstream signaling mechanisms triggering MyD88-mediated mTORC1 and inflammasome activation in macrophages following Ehrlichia infection. This study reveals that Ehrlichia-induced liver injury and toxic shock are mediated by MyD88-dependent inflammasome activation and autophagy inhibition.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kader</LastName>
<ForeName>Muhamuda</ForeName>
<Initials>M</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0001-8902-9296</Identifier>
<AffiliationInfo><Affiliation>Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Alaoui-El-Azher</LastName>
<ForeName>Mounia</ForeName>
<Initials>M</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-3209-5257</Identifier>
<AffiliationInfo><Affiliation>Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Vorhauer</LastName>
<ForeName>Jennie</ForeName>
<Initials>J</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-3897-6354</Identifier>
<AffiliationInfo><Affiliation>Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kode</LastName>
<ForeName>Bhushan B</ForeName>
<Initials>BB</Initials>
<AffiliationInfo><Affiliation>Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wells</LastName>
<ForeName>Jakob Z</ForeName>
<Initials>JZ</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0003-3530-8593</Identifier>
<AffiliationInfo><Affiliation>Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Stolz</LastName>
<ForeName>Donna</ForeName>
<Initials>D</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-1833-7010</Identifier>
<AffiliationInfo><Affiliation>Center for Biologic Imaging, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Michalopoulos</LastName>
<ForeName>George</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wells</LastName>
<ForeName>Alan</ForeName>
<Initials>A</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-1637-8150</Identifier>
<AffiliationInfo><Affiliation>Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Scott</LastName>
<ForeName>Melanie</ForeName>
<Initials>M</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0001-6864-5970</Identifier>
<AffiliationInfo><Affiliation>Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ismail</LastName>
<ForeName>Nahed</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>R01 GM102146</GrantID>
<Acronym>GM</Acronym>
<Agency>NIGMS NIH HHS</Agency>
<Country>United States</Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2017</Year>
<Month>10</Month>
<Day>19</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>PLoS Pathog</MedlineTA>
<NlmUniqueID>101238921</NlmUniqueID>
<ISSNLinking>1553-7366</ISSNLinking>
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<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D058847">Inflammasomes</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C507780">Myd88 protein, mouse</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D053594">Myeloid Differentiation Factor 88</NameOfSubstance>
</Chemical>
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<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D001343" MajorTopicYN="N">Autophagy</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015153" MajorTopicYN="N">Blotting, Western</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004536" MajorTopicYN="N">Ehrlichia</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016873" MajorTopicYN="N">Ehrlichiosis</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004797" MajorTopicYN="N">Enzyme-Linked Immunosorbent Assay</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005434" MajorTopicYN="N">Flow Cytometry</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005455" MajorTopicYN="N">Fluorescent Antibody Technique</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007091" MajorTopicYN="N">Image Processing, Computer-Assisted</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D020287" MajorTopicYN="N">In Situ Nick-End Labeling</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D058847" MajorTopicYN="N">Inflammasomes</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D017114" MajorTopicYN="N">Liver Failure, Acute</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
<QualifierName UI="Q000382" MajorTopicYN="Y">microbiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018345" MajorTopicYN="N">Mice, Knockout</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018613" MajorTopicYN="N">Microscopy, Confocal</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D046529" MajorTopicYN="N">Microscopy, Electron, Transmission</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D053594" MajorTopicYN="N">Myeloid Differentiation Factor 88</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D060888" MajorTopicYN="N">Real-Time Polymerase Chain Reaction</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D012772" MajorTopicYN="N">Shock, Septic</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
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	Serveur d'exploration sur la rapamycine et les champignons
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MyD88-dependent inflammasome activation and autophagy inhibition contributes to Ehrlichia-induced liver injury and toxic shock.

MyD88-dependent inflammasome activation and autophagy inhibition contributes to Ehrlichia-induced liver injury and toxic shock.

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