ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014
Role of protein kinase R in the killing of Leishmania major by macrophages in response to neutrophil elastase and TLR4 via TNFα and IFNβ.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- Cathepsin G and neutrophil elastase control Leishmania infantum parasitism through TLRs-dependent induction of IFN-α and TNF-α.Communications biology · 2026Article
- The dsRNA-dependent kinase (PKR) inhibits the growth ofParasitology · 2025Article
- Toll-Like Receptor 3 (TLR3) Is Engaged in the Intracellular Survival of the Protozoan ParasiteInfection and immunity · 2022Article
- Toll-Like Receptor- and Protein Kinase R-Induced Type I Interferon Sustains Infection ofFrontiers in immunology · 2022Article
- Role of the inhibitor of serine peptidase 2 (ISP2) of Trypanosoma brucei rhodesiense in parasite virulence and modulation of the inflammatory responses of the host.PLoS neglected tropical diseases · 2021Article
- Protein Kinase R in Bacterial Infections: Friend or Foe?Frontiers in immunology · 2021Review
- Kinins and Their Receptors in Infectious Diseases.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Translational profiling of macrophages infected with Leishmania donovani identifies mTOR- and eIF4A-sensitive immune-related transcripts.PLoS pathogens · 2020Article
- Neutrophil elastase promotesFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- TLR2 Signaling in Skin Nonhematopoietic Cells Induces Early Neutrophil Recruitment in Response to Leishmania major Infection.The Journal of investigative dermatology · 2019Article
- TLR4 Polymorphisms and Expression in Solid Cancers.Molecular diagnosis & therapy · 2018Review
- Emerging therapeutic targets for treatment of leishmaniasis.Expert opinion on therapeutic targets · 2018Review
- Inhibitor of serine peptidase 2 enhances Leishmania major survival in the skin through control of monocytes and monocyte-derived cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- The NOD2 receptor is crucial for immune responses towards New World Leishmania species.Scientific reports · 2017Article
- Disease severity in patients with visceral leishmaniasis is not altered by co-infection with intestinal parasites.PLoS neglected tropical diseases · 2017Article
- [Sivelestat alleviates nonalcoholic steatohepatitis in mice through inhibiting activation of Kupffer cells].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2017Article
- Function of Macrophage and Parasite Phosphatases in Leishmaniasis.Frontiers in immunology · 2017Review
- The Specific Protein Kinase R (PKR) Inhibitor C16 Protects Neonatal Hypoxia-Ischemia Brain Damages by Inhibiting Neuroinflammation in a Neonatal Rat Model.Medical science monitor : international medical journal of experimental and clinical research · 2016Article
- Visceral Leishmaniasis Patients Display Altered Composition and Maturity of Neutrophils as well as Impaired Neutrophil Effector Functions.Frontiers in immunology · 2016Article
- Leishmania Infection Engages Non-Receptor Protein Kinases Differentially to Persist in Infected Hosts.Frontiers in immunology · 2016Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
In cutaneous leishmaniasis, Leishmania amazonensis activates macrophage double-stranded, RNA-activated protein kinase R (PKR) to promote parasite growth. In our study, Leishmania major grew normally in RAW cells, RAW-expressing dominant-negative PKR (PKR-DN) cells, and macrophages of PKR-knockout mice, revealing that PKR is dispensable for L. major growth in macrophages. PKR activation in infected macrophages with poly I:C resulted in parasite death. Fifty percent of L. major-knockout lines for the ecotin-like serine peptidase inhibitor (ISP2; Δisp2/isp3), an inhibitor of neutrophil elastase (NE), died in RAW cells or macrophages from 129Sv mice, as a result of PKR activation. Inhibition of PKR or NE or neutralization of Toll-like receptor 4 or 2(TLR4 or TLR2) prevented the death of Δisp2/isp3. Δisp2/isp3 grew normally in RAW-PKR-DN cells or macrophages from 129Sv pkr(-/-), tlr2(-/-), trif(-/-), and myd88(-/-) mice, associating NE activity, PKR, and TLR responses with parasite death. Δisp2/isp3 increased the expression of mRNA for TNF-α by 2-fold and of interferon β (IFNβ) in a PKR-dependent manner. Antibodies to TNF-α reversed the 95% killing by Δisp2/isp3, whereas they grew normally in macrophages from IFN receptor-knockout mice. We propose that ISP2 prevents the activation of PKR via an NE-TLR4-TLR2 axis to control innate responses that contribute to the killing of L. major.-Faria, M. S., Calegari-Silva, T. C., de Carvalho Vivarini, A., Mottram, J. C., Lopes, U. G., Lima, A. P. C. A. Role of protein kinase R in the killing of Leishmania major by macrophages in response to neutrophil elastase and TLR4 via TNFα and IFNβ.
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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.