ArticleJournal of immunology (Baltimore, Md. : 1950)2014
STAT1 signaling is essential for protection against Cryptococcus neoformans infection in mice.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
58 citing papers in PubMed, 73 citations in OpenAlex.
- Blood neutrophil counts in HIV-infected patients with cryptococcal meningitis: Association with mortality.PloS one · 2018Trial
- MHC-I Upregulation and Increased Glucose Dependence Define Innate Antifungal Immune Responses to Cryptococcus neoformans.The Journal of infectious diseases · 2026Article
- Immune responses of different hosts toEuropean respiratory review : an official journal of the European Respiratory Society · 2025Review
- Clinical characteristics and prognostic factors of pulmonary and extrapulmonary cryptococcosis.BMC infectious diseases · 2024Article
- Cryptococcosis Associated With Biologic Therapy: A Narrative Review.Open forum infectious diseases · 2024Review
- Inbred Mouse Models inJournal of fungi (Basel, Switzerland) · 2024Review
- STAT1-Deficient HPV E6/E7-Associated Cancers Maintain Host Immunocompetency against Therapeutic Intervention.Vaccines · 2024Article
- Article
- Models for Inducing Experimental Cryptococcosis in Mice.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Detection and Quantification of Cryptococcus Uptake by Phagocytic Cells Using Imaging Flow Cytometry.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Development of animal models for emerging infectious diseases by breaking the barrier of species susceptibility to human pathogens.Emerging microbes & infections · 2023Article
- Cryptococcal meningitis.Nature reviews. Disease primers · 2023Review
- Article
- Innate Pulmonary Phagocytes and Their Interactions with PathogenicJournal of fungi (Basel, Switzerland) · 2023Review
- Regulation of macrophage IFNγ-stimulated gene expression by the transcriptional coregulator CITED1.Journal of cell science · 2023Article
- Vaccine protection by Cryptococcus neoformans Δsgl1 is mediated by γδ T cells via TLR2 signaling.Mucosal immunology · 2022Article
- Macrophage Mediated Immunomodulation DuringFrontiers in cellular and infection microbiology · 2022Review
- Corticosteroid insensitivity persists in the absence of STAT1 signaling in severe allergic airway inflammation.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Murine Inducible Nitric Oxide Synthase Expression Is Essential for Antifungal Defenses in Kidneys during DisseminatedJournal of immunology (Baltimore, Md. : 1950) · 2021Article
- X-linked immunodeficient (XID) mice exhibit high susceptibility to Cryptococcus gattii infection.Scientific reports · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Nonprotective immune responses to highly virulent Cryptococcus neoformans strains, such as H99, are associated with Th2-type cytokine production, alternatively activated macrophages, and inability of the host to clear the fungus. In contrast, experimental studies show that protective immune responses against cryptococcosis are associated with Th1-type cytokine production and classical macrophage activation. The protective response induced during C. neoformans strain H99γ (C. neoformans strain H99 engineered to produce murine IFN-γ) infection correlates with enhanced phosphorylation of the transcription factor STAT1 in macrophages; however, the role of STAT1 in protective immunity to C. neoformans is unknown. The current studies examined the effect of STAT1 deletion in murine models of protective immunity to C. neoformans. Survival and fungal burden were evaluated in wild-type and STAT1 knockout (KO) mice infected with either strain H99γ or C. neoformans strain 52D (unmodified clinical isolate). Both strains H99γ and 52D were rapidly cleared from the lungs, did not disseminate to the CNS, or cause mortality in the wild-type mice. Conversely, STAT1 KO mice infected with H99γ or 52D had significantly increased pulmonary fungal burden, CNS dissemination, and 90-100% mortality. STAT1 deletion resulted in a shift from Th1 to Th2 cytokine bias, pronounced lung inflammation, and defective classical macrophage activation. Pulmonary macrophages from STAT1 KO mice exhibited defects in NO production correlating with inefficient inhibition of fungal proliferation. These studies demonstrate that STAT1 signaling is essential not only for regulation of immune polarization but also for the classical activation of macrophages that occurs during protective anticryptococcal immune responses.
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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.