ArticleJournal of immunology (Baltimore, Md. : 1950)2012
IFN-γ-producing CD4+ T cells promote experimental cerebral malaria by modulating CD8+ T cell accumulation within the brain.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 1 of them a synthesis that pooled it.
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Who cites it
111 citing papers in PubMed, 1 synthesis or guideline pooled it, 169 citations in OpenAlex.
- Plasmodium and intestinal parasite perturbations of the infected host's inflammatory responses: a systematic review.Parasites & vectors · 2018Pooled it
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- Exploring the relationship between lipid metabolism and cognition in individuals living with stable-phase Schizophrenia: a small cross-sectional study using Olink proteomics analysis.BMC psychiatry · 2024Article
- Asymptomatic Low-Density Plasmodium falciparum Infections: Parasites Under the Host's Immune Radar?The Journal of infectious diseases · 2024Review
- Discrete class I molecules on brain endothelium differentially regulate neuropathology in experimental cerebral malaria.Brain : a journal of neurology · 2024Article
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- CD4 T Cell-Dependent and -Independent Roles for IFN-γ in Blood-Stage Malaria.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- The Complexity of Interferon Signaling in Host Defense against Protozoan Parasite Infection.Pathogens (Basel, Switzerland) · 2023Review
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- Pathophysiology of Cerebral Malaria: Implications of MSCs as A Regenerative Medicinal Tool.Bioengineering (Basel, Switzerland) · 2022Review
- Hypothyroidism confers tolerance to cerebral malaria.Science advances · 2022Article
- Comparative transcriptomic analysis reveals translationally relevant processes in mouse models of malaria.eLife · 2022Article
- Forward Genetics in Apicomplexa Biology: The Host Side of the Story.Frontiers in cellular and infection microbiology · 2022Review
- Review
- The gut-immune-brain axis in neurodevelopment and neurological disorders.Microbiome research reports · 2022Review
- Memory CD8Immunology · 2021Article
- 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
- The plasma membrane calcium ATPase 4 does not influence parasite levels but partially promotes experimental cerebral malaria during murine blood stage malaria.Malaria journal · 2021Article
51 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
It is well established that IFN-γ is required for the development of experimental cerebral malaria (ECM) during Plasmodium berghei ANKA infection of C57BL/6 mice. However, the temporal and tissue-specific cellular sources of IFN-γ during P. berghei ANKA infection have not been investigated, and it is not known whether IFN-γ production by a single cell type in isolation can induce cerebral pathology. In this study, using IFN-γ reporter mice, we show that NK cells dominate the IFN-γ response during the early stages of infection in the brain, but not in the spleen, before being replaced by CD4(+) and CD8(+) T cells. Importantly, we demonstrate that IFN-γ-producing CD4(+) T cells, but not innate or CD8(+) T cells, can promote the development of ECM in normally resistant IFN-γ(-/-) mice infected with P. berghei ANKA. Adoptively transferred wild-type CD4(+) T cells accumulate within the spleen, lung, and brain of IFN-γ(-/-) mice and induce ECM through active IFN-γ secretion, which increases the accumulation of endogenous IFN-γ(-/-) CD8(+) T cells within the brain. Depletion of endogenous IFN-γ(-/-) CD8(+) T cells abrogates the ability of wild-type CD4(+) T cells to promote ECM. Finally, we show that IFN-γ production, specifically by CD4(+) T cells, is sufficient to induce expression of CXCL9 and CXCL10 within the brain, providing a mechanistic basis for the enhanced CD8(+) T cell accumulation. To our knowledge, these observations demonstrate, for the first time, the importance of and pathways by which IFN-γ-producing CD4(+) T cells promote the development of ECM during P. berghei ANKA infection.
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