ArticlePLoS pathogens2017
TNF signalling drives expansion of bone marrow CD4+ T cells responsible for HSC exhaustion in experimental visceral leishmaniasis.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Modulation of haematopoiesis by protozoal and helminth parasites.Parasite immunology · 2023Review
- Field-Deployable Treatments For Leishmaniasis: Intrinsic Challenges, Recent Developments and Next Steps.Research and reports in tropical medicine · 2023Review
- Long-term hematopoietic stem cells as a parasite niche during treatment failure in visceral leishmaniasis.Communications biology · 2022Article
- Persistent CutaneousMicroorganisms · 2022Article
- Bone marrow remodeling supports hematopoiesis in response to immune thrombocytopenia progression in mice.Blood advances · 2021Article
- Dissecting pathways to thrombocytopenia in a mouse model of visceral leishmaniasis.Blood advances · 2021Article
- Role of Cytokines in Experimental and Human Visceral Leishmaniasis.Frontiers in cellular and infection microbiology · 2021Review
- Hematological consequences of malaria in mice previously treated for visceral leishmaniasis.Wellcome open research · 2021Article
- Interferon-γ-Producing CD4Frontiers in immunology · 2021Article
- Leishmaniasis immunopathology-impact on design and use of vaccines, diagnostics and drugs.Seminars in immunopathology · 2020Review
- Establishment, optimisation and quantitation of a bioluminescent murine infection model of visceral leishmaniasis for systematic vaccine screening.Scientific reports · 2020Article
- Multilevel defects in the hematopoietic niche in essential thrombocythemia.Haematologica · 2020Article
- Unexpected encounter of the parasitic kind.World journal of stem cells · 2019Review
- Association between Insulin-Like Growth Factor-I Levels and the Disease Progression and Anemia in Visceral Leishmaniasis.The American journal of tropical medicine and hygiene · 2019Article
- CD4Frontiers in immunology · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Visceral leishmaniasis is associated with significant changes in hematological function but the mechanisms underlying these changes are largely unknown. In contrast to naïve mice, where most long-term hematopoietic stem cells (LT-HSCs; LSK CD150+ CD34- CD48- cells) in bone marrow (BM) are quiescent, we found that during Leishmania donovani infection most LT-HSCs had entered cell cycle. Loss of quiescence correlated with a reduced self-renewal capacity and functional exhaustion, as measured by serial transfer. Quiescent LT-HSCs were maintained in infected RAG2 KO mice, but lost following adoptive transfer of IFNγ-sufficient but not IFNγ-deficient CD4+ T cells. Using mixed BM chimeras, we established that IFNγ and TNF signalling pathways converge at the level of CD4+ T cells. Critically, intrinsic TNF signalling is required for the expansion and/or differentiation of pathogenic IFNγ+CD4+ T cells that promote the irreversible loss of BM function. These findings provide new insights into the pathogenic potential of CD4+ T cells that target hematopoietic function in leishmaniasis and perhaps other infectious diseases where TNF expression and BM dysfunction also occur simultaneously.
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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.