ArticlePLoS pathogens2015
Paradoxical Immune Responses in Non-HIV Cryptococcal Meningitis.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
106 citing papers in PubMed, 1 synthesis or guideline pooled it, 164 citations in OpenAlex.
- Global guideline for the diagnosis and management of cryptococcosis: an initiative of the ECMM and ISHAM in cooperation with the ASM.The Lancet. Infectious diseases · 2024Guideline
- Exhausted T cell phenotypes in disseminated coccidioidomycosis.JCI insight · 2026Article
- Cerebral Venous Thrombosis in Previously Healthy Patients with Cryptococcal Meningitis.The Journal of infectious diseases · 2026Article
- Corticosteroid Therapy and Long-Term Outcomes of Post-Infectious Inflammatory Syndrome in Non-HIV Immunosuppressed Cryptococcal Meningitis: A Multicenter Case Series.The Journal of infectious diseases · 2026Article
- Clinical spectrum, immune status, and prognostic factors of cryptococcosis: insights from a large, multi-center, ambispective cohort study in southeastern China.Infectious diseases of poverty · 2026Article
- Advances in cryptococcal infections-associated immunopathology and potential therapeutic strategies.Frontiers in pharmacology · 2026Review
- Cryptococcal Meningitis Treatment Beyond HIV: Recognizing the Need for Individualized Immune-Based Strategies.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025Article
- The Pain Is in the Brain With the Sugar-Coated Killer.The Journal of infectious diseases · 2025Review
- Foxp3Research square · 2025Article
- Peripheral blood CD4The Journal of infection · 2025Article
- Pathway-instructed therapeutic selection of ruxolitinib reduces neuroinflammation in fungal postinfectious inflammatory syndrome.Science advances · 2025Observational
- Research progress on immunometabolism and gut microbiota in cryptococcal meningitis: mechanisms and therapeutic implications.Frontiers in neuroscience · 2025Review
- Article
- Cerebrospinal Fluid Lactate Levels as a Prognostic Indicator in Patients With Cryptococcal Meningitis Who Are HIV Negative: A Retrospective Cohort Study.Open forum infectious diseases · 2024Article
- Mechanisms and Virulence Factors ofJournal of fungi (Basel, Switzerland) · 2024Review
- Molecular Diagnostics ofDiseases (Basel, Switzerland) · 2024Review
- JAK/STAT Signaling Predominates in Human and Murine Fungal Post-infectious Inflammatory Response Syndrome.medRxiv : the preprint server for health sciences · 2024Article
- The emerging links between immunosenescence in innate immune system and neurocryptococcosis.Frontiers in immunology · 2024Review
- Case report: A diabetic patient with cryptococcal meningoencephalitis complicated by post-infectious inflammatory response syndrome.Frontiers in immunology · 2024Article
- Tocilizumab as a Potential Adjunctive Therapy to Corticosteroids in Cryptococcal Post-infectious Inflammatory Response Syndrome (PIIRS): a Report of Two Cases.Journal of clinical immunology · 2023Article
46 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 8 institutions in 2 countries.
Funding
Abstract
The fungus Cryptococcus is a major cause of meningoencephalitis in HIV-infected as well as HIV-uninfected individuals with mortalities in developed countries of 20% and 30%, respectively. In HIV-related disease, defects in T-cell immunity are paramount, whereas there is little understanding of mechanisms of susceptibility in non-HIV related disease, especially that occurring in previously healthy adults. The present description is the first detailed immunological study of non-HIV-infected patients including those with severe central nervous system (s-CNS) disease to 1) identify mechanisms of susceptibility as well as 2) understand mechanisms underlying severe disease. Despite the expectation that, as in HIV, T-cell immunity would be deficient in such patients, cerebrospinal fluid (CSF) immunophenotyping, T-cell activation studies, soluble cytokine mapping and tissue cellular phenotyping demonstrated that patients with s-CNS disease had effective microbiological control, but displayed strong intrathecal expansion and activation of cells of both the innate and adaptive immunity including HLA-DR+ CD4+ and CD8+ cells and NK cells. These expanded CSF T cells were enriched for cryptococcal-antigen specific CD4+ cells and expressed high levels of IFN-γ as well as a lack of elevated CSF levels of typical T-cell specific Th2 cytokines -- IL-4 and IL-13. This inflammatory response was accompanied by elevated levels of CSF NFL, a marker of axonal damage, consistent with ongoing neurological damage. However, while tissue macrophage recruitment to the site of infection was intact, polarization studies of brain biopsy and autopsy specimens demonstrated an M2 macrophage polarization and poor phagocytosis of fungal cells. These studies thus expand the paradigm for cryptococcal disease susceptibility to include a prominent role for macrophage activation defects and suggest a spectrum of disease whereby severe neurological disease is characterized by immune-mediated host cell damage.
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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.