ArticleJournal of immunology (Baltimore, Md. : 1950)2007
Activation of the MAPK, ERK, following Leishmania amazonensis infection of macrophages.
Article in Journal of immunology (Baltimore, Md. : 1950), 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 120 citations in OpenAlex.
- Dual host and pathogen targeting by MEK1/2 inhibitors.Infection and immunity · 2026Review
- Chemical degradation of Human p38-MAPK reveals it as a potential host target to combat parasitic infections by Leishmania donovani and Plasmodium falciparum.Communications biology · 2026Article
- Sphingosine-1-phosphate receptor signaling regulates an ERK1/2-p65 molecular switch in macrophages duringFrontiers in pharmacology · 2026Article
- Epigenetic landscape of Leishmania-host interactions.Epigenomics · 2025Review
- Leishmania amazonensis infection induces PD-L1 expression on dendritic cells and impairs Th1 responses in vitro and in vivo.Scientific reports · 2025Article
- Epigenetic paradigms/exemplars of the macrophage: inflammasome axis in Leishmaniasis.Molecular and cellular biochemistry · 2022Review
- Temporary Shutdown of ERK1/2 Phosphorylation Is Associated With Activation of Adaptive Immune Cell Responses and Disease Progression DuringFrontiers in immunology · 2022Article
- Comparative transcriptomic analysis of long noncoding RNAs inFrontiers in genetics · 2022Article
- Dissection of the macrophage response towards infection by theFrontiers in cellular and infection microbiology · 2022Article
- Network-Based Approaches Reveal Potential Therapeutic Targets for Host-Directed Antileishmanial Therapy Driving Drug Repurposing.Microbiology spectrum · 2021Article
- Potential biomarkers of immune protection in human leishmaniasis.Medical microbiology and immunology · 2021Review
- Inoculation of theMicroorganisms · 2021Article
- Computational System Level Approaches for Discerning Reciprocal Regulation of IL10 and IL12 in Leishmaniasis.Frontiers in genetics · 2021Article
- The Paradox of a Phagosomal Lifestyle: How Innate Host Cell-Frontiers in immunology · 2021Review
- Immune Complex-Driven Generation of Human Macrophages with Anti-Inflammatory and Growth-Promoting Activity.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Protective Functions of Reactive Astrocytes Following Central Nervous System Insult.Frontiers in immunology · 2020Review
- Article
- Obesity impairs resistance to Leishmania major infection in C57BL/6 mice.PLoS neglected tropical diseases · 2020Article
- Differential immune response modulation in early Leishmania amazonensis infection of BALB/c and C57BL/6 macrophages based on transcriptome profiles.Scientific reports · 2019Article
- Metabolomic Profile of BALB/c Macrophages Infected withInternational journal of molecular sciences · 2019Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
IL-10 is a critical cytokine in determining host susceptibility to Leishmania spp. We previously demonstrated that macrophage-derived IL-10 could contribute to disease exacerbation, but the mechanisms whereby Leishmania infections led to IL-10 induction were not fully understood. In this study, we demonstrated that infection of macrophages with Leishmania amazonensis amastigotes led to the activation of the MAPK, ERK1/2. This activation was required, but not sufficient for IL-10 induction. In addition to ERK activation, an inflammatory stimulus, such as low m.w. hyaluronic acid from the extracellular matrix, must also be present. The combination of these two signals resulted in the superinduction of IL-10. We also demonstrated that IgG on the surface of Leishmania amastigotes was required to achieve maximal IL-10 production from infected macrophages. Surface IgG engages macrophage FcgammaR to induce ERK activation. Macrophages lacking FcgammaR, or macrophages treated with an inhibitor of spleen tyrosine kinase, the tyrosine kinase that signals via FcgammaR, failed to activate ERK and consequently failed to produce IL-10 following infection with Leishmania amastigotes. We confirmed that ERK1/2 activation led to the phosphorylation of histone H3 at the IL-10 promoter, and this phosphorylation allowed for the binding of the transcription factor, Sp1, to the IL-10 promoter. Finally, the administration of U0126, an inhibitor of ERK activation, to infected mice resulted in decreased lesion progression with reduced numbers of parasites in them. Thus, our findings reveal an important role of MAPK, ERK signaling in the pathogenesis of Leishmania infection.
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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.