ArticleThe Journal of biological chemistry2015
Phagosomal Acidification Prevents Macrophage Inflammatory Cytokine Production to Malaria, and Dendritic Cells Are the Major Source at the Early Stages of Infection: IMPLICATION FOR MALARIA PROTECTIVE IMMUNITY DEVELOPMENT.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Alterations in von Willebrand Factor Levels in Patients with Malaria: A Systematic Review and Meta-Analysis of Disease Severity.Medicina (Kaunas, Lithuania) · 2025Pooled it
- E3 Ubiquitin Ligase RNF13 Suppresses TLR Lysosomal Degradation by Promoting LAMP-1 Proteasomal Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Trained immunity: a cutting edge approach for designing novel vaccines against parasitic diseases?Frontiers in immunology · 2023Review
- Lipopolysaccharide Preconditioning Augments Phagocytosis of Malaria-Parasitized Red Blood Cells by Bone Marrow-Derived Macrophages in the Liver, Thereby Increasing the Murine Survival after Plasmodium yoelii Infection.Infection and immunity · 2021Article
- Activity of Lymphostatin, A Lymphocyte Inhibitory Virulence Factor of Pathogenic Escherichia coli, is Dependent on a Cysteine Protease Motif.Journal of molecular biology · 2021Article
- Recent Advances in Understanding the Inflammatory Response in Malaria: A Review of the Dual Role of Cytokines.Journal of immunology research · 2021Review
- Lessons Learned for Pathogenesis, Immunology, and Disease of Erythrocytic Parasites:Frontiers in cellular and infection microbiology · 2021Review
- The host targeting effect of chloroquine in malaria.Current opinion in immunology · 2020Review
- Type I Interferons and Malaria: A Double-Edge Sword Against a Complex Parasitic Disease.Frontiers in cellular and infection microbiology · 2020Review
- IL-10-Dependent Crosstalk between Murine Marginal Zone B Cells, Macrophages, and CD8αImmunity · 2019Article
- Circulating Monocytes, Tissue Macrophages, and Malaria.Journal of tropical medicine · 2019Review
- A malaria protein factor induces IL-4 production by dendritic cells via PI3K-Akt-NF-κB signaling independent of MyD88/TRIF and promotes Th2 response.The Journal of biological chemistry · 2018Article
- Parasite Recognition and Signaling Mechanisms in Innate Immune Responses to Malaria.Frontiers in immunology · 2018Review
- Small molecule-based inhibition of MEK1/2 proteins dampens inflammatory responses to malaria, reduces parasite load, and mitigates pathogenic outcomes.The Journal of biological chemistry · 2017Article
- CD36 receptor regulates malaria-induced immune responses primarily at early blood stage infection contributing to parasitemia control and resistance to mortality.The Journal of biological chemistry · 2017Article
- Cytokines and Chemokines in Cerebral Malaria Pathogenesis.Frontiers in cellular and infection microbiology · 2017Review
- Interaction betweenFrontiers in cellular and infection microbiology · 2017Article
- Cannabinoid Receptor 2 Modulates Susceptibility to Experimental Cerebral Malaria through a CCL17-dependent Mechanism.The Journal of biological chemistry · 2016Article
- Gymnema inodorum Leaf Extract Improves Cardiac Function in Experimental Mice Infected with Plasmodium Berghei.Journal of evidence-based integrative medicineArticle
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Inflammatory cytokines produced at the early stages of malaria infection contribute to shaping protective immunity and pathophysiology. To gain mechanistic insight into these processes, it is important to understand the cellular origin of cytokines because both cytokine input and cytokine-producing cells play key roles. Here, we determined cytokine responses by monocytes, macrophages, and dendritic cells (DCs) to purified Plasmodium falciparum and Plasmodium berghei ANKA, and by spleen macrophages and DCs from Plasmodium yoelii 17NXL-infected and P. berghei ANKA-infected mice. The results demonstrate that monocytes and macrophages do not produce inflammatory cytokines to malaria parasites and that DCs are the primary source early in infection, and DC subsets differentially produce cytokines. Importantly, blocking of phagosomal acidification by inhibiting vacuolar-type H(+)-ATPase enabled macrophages to elicit cytokine responses. Because cytokine responses to malaria parasites are mediated primarily through endosomal Toll-like receptors, our data indicate that the inability of macrophages to produce cytokines is due to the phagosomal acidification that disrupts endosomal ligand-receptor engagement. Macrophages efficiently produced cytokines to LPS upon simultaneously internalizing parasites and to heat-killed Escherichia coli, demonstrating that phagosomal acidification affects endosomal receptor-mediated, but not cell surface receptor-mediated, recognition of Toll-like receptor agonists. Enabling monocytes/macrophages to elicit immune responses to parasites by blocking endosomal acidification can be a novel strategy for the effective development of protective immunity to malaria. The results have important implications for enhancing the efficacy of a whole parasite-based malaria vaccine and for designing strategies for the development of protective immunity to pathogens that induce immune responses primarily through endosomal receptors.
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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.