ArticlePLoS pathogens2016
The Prostaglandin E2-EP3 Receptor Axis Regulates Anaplasma phagocytophilum-Mediated NLRC4 Inflammasome Activation.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Obligate intracellular bacteria and host cell death pathways-the matter of life and death.Cell and tissue research · 2025Review
- Innate immune mechanisms of infection: what we know and potential conserved mechanisms affecting sleep during infection.Neurobiology of sleep and circadian rhythms · 2025Article
- NLRC4, inflammation and colorectal cancer (Review).International journal of oncology · 2024Review
- Human and mouse NAIP/NLRC4 inflammasome responses to bacterial infection.Current opinion in microbiology · 2023Review
- Innate immunity in rickettsial infections.Frontiers in cellular and infection microbiology · 2023Review
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- DDX17 is an essential mediator of sterile NLRC4 inflammasome activation by retrotransposon RNAs.Science immunology · 2021Article
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- Roles of Eicosanoids in Regulating Inflammation and Neutrophil Migration as an Innate Host Response to Bacterial Infections.Infection and immunity · 2021Article
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- KLK3 SNP-SNP interactions for prediction of prostate cancer aggressiveness.Scientific reports · 2021Article
- Pattern Recognition Receptors in Innate Immunity to Obligate Intracellular Bacteria.Zoonoses (Shannon, Ireland) · 2021Article
- Updating the NLRC4 Inflammasome: from Bacterial Infections to Autoimmunity and Cancer.Frontiers in immunology · 2021Review
- Emerging Roles of Autophagy and Inflammasome in Ehrlichiosis.Frontiers in immunology · 2019Review
- Thrombospondin-1 interactions regulate eicosanoid metabolism and signaling in cancer-related inflammation.Cancer metastasis reviews · 2018Review
- Differential Susceptibility of Male Versus Female Laboratory Mice toTropical medicine and infectious disease · 2018Article
- The NLRC4 Inflammasome.Immunological reviews · 2018Review
- Alternative Splicing of Differentiated Myeloid Cell Transcripts after Infection byFrontiers in cellular and infection microbiology · 2018Article
- Article
- Inflammasomes: Pandora's box for sepsis.Journal of inflammation research · 2018Review
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 2 countries.
Funding
Abstract
Rickettsial agents are sensed by pattern recognition receptors but lack pathogen-associated molecular patterns commonly observed in facultative intracellular bacteria. Due to these molecular features, the order Rickettsiales can be used to uncover broader principles of bacterial immunity. Here, we used the bacterium Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis, to reveal a novel microbial surveillance system. Mechanistically, we discovered that upon A. phagocytophilum infection, cytosolic phospholipase A2 cleaves arachidonic acid from phospholipids, which is converted to the eicosanoid prostaglandin E2 (PGE2) via cyclooxygenase 2 (COX2) and the membrane associated prostaglandin E synthase-1 (mPGES-1). PGE2-EP3 receptor signaling leads to activation of the NLRC4 inflammasome and secretion of interleukin (IL)-1β and IL-18. Importantly, the receptor-interacting serine/threonine-protein kinase 2 (RIPK2) was identified as a major regulator of the immune response against A. phagocytophilum. Accordingly, mice lacking COX2 were more susceptible to A. phagocytophilum, had a defect in IL-18 secretion and exhibited splenomegaly and damage to the splenic architecture. Remarkably, Salmonella-induced NLRC4 inflammasome activation was not affected by either chemical inhibition or genetic ablation of genes associated with PGE2 biosynthesis and signaling. This divergence in immune circuitry was due to reduced levels of the PGE2-EP3 receptor during Salmonella infection when compared to A. phagocytophilum. Collectively, we reveal the existence of a functionally distinct NLRC4 inflammasome illustrated by the rickettsial agent A. phagocytophilum.
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Registered trials
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.