ArticlePLoS pathogens2017
MyD88-dependent inflammasome activation and autophagy inhibition contributes to Ehrlichia-induced liver injury and toxic shock.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 69 citations in OpenAlex.
- Host mitochondrial DNA in bacterial pathogenesis: Friend, Foe, or Both?Archives of microbiology · 2026Review
- Obligate intracellular bacteria and host cell death pathways-the matter of life and death.Cell and tissue research · 2025Review
- Attenuation of Pulmonary Fibrosis by the MyD88 Inhibitor TJ-M2010-5 Through Autophagy Induction in Mice.Biomedicines · 2025Article
- Oxidative stress responses inmBio · 2025Review
- Non-Canonical Inflammasome Pathway: The Role of Cell Death and Inflammation in Ehrlichiosis.Cells · 2023Review
- Evasion of host antioxidative response via disruption of NRF2 signaling in fatal Ehrlichia-induced liver injury.PLoS pathogens · 2023Article
- Mitochondrial Dysfunction in Bacterial Infections.Pathogens (Basel, Switzerland) · 2023Review
- Role of Autophagy inCells · 2023Article
- Hepatocyte-specific regulation of autophagy and inflammasome activation via MyD88 during lethalFrontiers in immunology · 2023Article
- Review: Protective Immunity and Immunopathology of Ehrlichiosis.Zoonoses (Shannon, Ireland) · 2022Article
- Apoptosis and Autophagy: Current Understanding in Tick-Pathogen Interactions.Frontiers in cellular and infection microbiology · 2022Review
- miR-340-5p Alleviates Oxidative Stress Injury by Targeting MyD88 in Sepsis-Induced Cardiomyopathy.Oxidative medicine and cellular longevity · 2022Article
- IL-18R-mediated HSC quiescence and MLKL-dependent cell death limit hematopoiesis during infection-induced shock.Stem cell reports · 2021Article
- The Liver and the Hepatic Immune Response inPathogens (Basel, Switzerland) · 2021Review
- Mutations in Ehrlichia chaffeensis Genes ECH_0660 and ECH_0665 Cause Transcriptional Changes in Response to Zinc or Iron Limitation.Journal of bacteriology · 2021Article
- Inhibition of heat shock protein 90 alleviates cholestatic liver injury by decreasing IL-1β and IL-18 expression.Experimental and therapeutic medicine · 2021Article
- Comparative Analysis of Genome of Ehrlichia sp. HF, a Model Bacterium to Study Fatal Human Ehrlichiosis.BMC genomics · 2021Article
- Article
- Pattern Recognition Receptors in Innate Immunity to Obligate Intracellular Bacteria.Zoonoses (Shannon, Ireland) · 2021Article
- Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities.Cellular & molecular immunology · 2021Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.