ArticleThe Journal of experimental medicine2008
Inhibition of histamine-mediated signaling confers significant protection against severe malaria in mouse models of disease.
Article in The Journal of experimental medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed.
- Article
- LRO biogenesis and function: what can we learn from mast cells?Frontiers in cell and developmental biology · 2025Review
- The type 2 immune response in gut homeostasis and parasite transmission in malaria.Trends in parasitology · 2025Review
- Pathogenetic mechanisms and treatment targets in cerebral malaria.Nature reviews. Neurology · 2023Review
- Evaluation of xanthene-appended quinoline hybrids as potential leads against antimalarial drug targets.Molecular diversity · 2023Article
- Article
- Mast cell-mediated immune regulation in health and disease.Frontiers in medicine · 2023Review
- Histamine: A Mediator of Intestinal Disorders-A Review.Metabolites · 2022Review
- Live Vaccination with Blood-StageVaccines · 2022Article
- Malaria-induced bacteremia as a consequence of multiple parasite survival strategies.Current research in microbial sciences · 2021Review
- Histamine Ingestion byBiomolecules · 2021Article
- Nonlethal Plasmodium yoelii Infection Drives Complex Patterns of Th2-Type Host Immunity and Mast Cell-Dependent Bacteremia.Infection and immunity · 2020Article
- Effects of centrifugation and whole-body vibrations on blood-brain barrier permeability in mice.NPJ microgravity · 2020Article
- Article
- Genetic analysis of cerebral malaria in the mouse model infected with Plasmodium berghei.Mammalian genome : official journal of the International Mammalian Genome Society · 2018Review
- Impact of polyphenols on mast cells with special emphasis on the effect of quercetin and luteolin.Central-European journal of immunology · 2018Review
- Immunological memory to blood-stage malaria infection is controlled by the histamine releasing factor (HRF) of the parasite.Scientific reports · 2017Article
- The antimicrobial molecule trappin-2/elafin has anti-parasitic properties and is protective in vivo in a murine model of cerebral malaria.Scientific reports · 2017Article
- The Roles of Mast Cells in Parasitic Protozoan Infections.Frontiers in immunology · 2017Review
- Role of basophils in protective immunity to parasitic infections.Seminars in immunopathology · 2016Review
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
From the inoculation of Plasmodium sporozoites via Anopheles mosquito bites to the development of blood-stage parasites, a hallmark of the host response is an inflammatory reaction characterized by elevated histamine levels in the serum and tissues. Given the proinflammatory and immunosuppressive activities associated with histamine, we postulated that this vasoactive amine participates in malaria pathogenesis. Combined genetic and pharmacologic approaches demonstrated that histamine binding to H1R and H2R but not H3R and H4R increases the susceptibility of mice to infection with Plasmodium. To further understand the role of histamine in malaria pathogenesis, we used histidine decarboxylase-deficient (HDC(-/-)) mice, which are free of histamine. HDC(-/-) mice were highly resistant to severe malaria whether infected by mosquito bites or via injection of infected erythrocytes. HDC(-/-) mice displayed resistance to two lethal strains: Plasmodium berghei (Pb) ANKA, which triggers cerebral malaria (CM), and Pb NK65, which causes death without neurological symptoms. The resistance of HDC(-/-) mice to CM was associated with preserved blood-brain barrier integrity, the absence of infected erythrocyte aggregation in the brain vessels, and a lack of sequestration of CD4 and CD8 T cells. We demonstrate that histamine-mediated signaling contributes to malaria pathogenesis. Understanding the basis for these biological effects of histamine during infection may lead to novel therapeutic strategies to alleviate the severity of malaria.
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