Cryptococcus neoformans Infection in the Central Nervous System: The Battle between Host and Pathogen

Chen, Yanli; Shi, Zoe W.; Strickland, Ashley B.; Shi, Meiqing

doi:10.3390/jof8101069

Cited by 39 publications

(30 citation statements)

References 220 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As the proboscis traverses the brain, dissolving the proboscis cuticle would provide B. bassiana a direct route to the brain. Similarly, fungi also invade the human brain (Cannon and Gruenheid, 2022, Chen et al, 2022, Pisa et al, 2020, Pisa et al, 2015a, Pisa et al, 2015b). The most common infection is by Cryptococcus , which causes meningoencephalitis, and Cryptococcus enters the human brain through the nose, by inhalation, followed by degradation of the BBB (Chen et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Fungi activate Toll-1 dependent immune evasion to induce cell loss in the host brain

Singh,

Roberts,

Moraga

et al. 2024

Preprint

View full text Add to dashboard Cite

Fungi evolve within the host, ensuring their own nutrition and reproduction, at the expense of host health. They intervene in hosts brain function, to alter host behaviour and induce neurodegeneration. In humans, fungal infections are emerging as drivers of neuroinflammation, neurodegenerative diseases and psychiatric disorders. However, how fungi alter the host brain is unknown. Fungi trigger an innate immune response mediated by the Toll-1/TLR receptor, the adaptor MyD88 and the transcription factor Dif/NFkB, that induce the expression of antimicrobial peptides (AMPs). However, in the nervous system, Toll-1/TLR could also drive an alternative pathway involving the adaptor Sarm, which causes cell death instead. Sarm is the universal inhibitor of MyD88 and could drive immune evasion. The entomopathogenic fungus Beauveria bassiana is well-known to activate Toll-1 signalling in innate immunity in Drosophila. In fruit-flies, the adaptor Wek links Toll-1 to Sarm. Thus, here we asked whether B. bassiana could damage the Drosophila brain via Toll-1, Wek and Sarm. We show that exposure to B. bassiana reduced fly lifespan and impaired locomotion. B. bassiana entered the brain and induced the up-regulation of AMPs, as well as wek and sarm, within the brain. Exposure to B. bassiana caused neuronal and glial loss in the adult Drosophila brain. Importantly, RNAi knockdown of Toll-1, wek or sarm concomitantly with infection prevented B. bassiana induced cell loss. By contrast, over-expression of wek or sarm was sufficient to cause dopaminergic neuron loss in the absence of infection. These data show that B. bassiana caused cell loss in the host brain via Toll-1/Wek/Sarm signalling driving immune evasion. We conclude that pathogens can benefit from an innate immunity receptor to damage the host brain. A similar activation of Sarm downstream of TLRs in response to fungal infections could underlie psychiatric and neurodegenerative diseases in humans.

show abstract

Section: Discussionmentioning

confidence: 99%

Fungi activate Toll-1 dependent immune evasion to induce cell loss in the host brain

Singh,

Roberts,

Moraga

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…In the event of Cryptococcus infection, CD4+/CD8+ T lymphocytes produce IFN-γ that promotes the fungicidal activity of macrophages, which is a necessary response to control the disease. In this case series, we hypothesized that this CD4+ T lymphocytopenia-associated SARS-CoV-2 infection could increase the risk of cerebral cryptococcosis [ 12 ]. Likewise, these values were normalized in patients who obtained control of CD4+/CD8+ T lymphocytes after discharge, suggesting the transient effect produced by SARS-CoV-2 infection ( Figure 2 ).…”

Section: Discussionmentioning

confidence: 99%

Cerebral Cryptococcosis Associated with CD4+ T-lymphocytopenia in Non-HIV Patients after SARS-CoV-2 Infection: Case Series in a Specialized Institute in Lima, Peru

et al. 2023

View full text Add to dashboard Cite

Cases of cryptococcosis have been reported in patients with COVID-19. The majority are in patients with severe symptoms or who received immunosuppressants. However, there is still no clear association between COVID-19 and cryptococcosis. We report eight cases of cerebral cryptococcosis associated with CD4+ T lymphocytopenia in non-HIV patients after SARS-CoV-2 infection. The median age was 57 years and 5/8 were male. In addition, 2/8 of patients had diabetes, and 8/8 had a history of mild COVID-19, with a median of 75 days before diagnosis of cerebral cryptococcosis. All patients denied having received prior immunosuppressive therapy. The most frequent symptoms were confusion (8/8), headache (7/8), vomiting (6/8), and nausea (6/8) All patients were diagnosed by isolating Cryptococcus in cerebrospinal fluid. The median CD4+ and CD8+ T lymphocytes were 247 and 173.5, respectively. Other causes of immunosuppression, such as HIV or HTLV infection, were excluded in all patients. Finally, three patients died, and one presented long-term visual and auditory sequelae. The CD4+/CD8+ T lymphocyte count normalized during follow-up in those patients who survived. We hypothesize that CD4+ T lymphocytopenia in the patients in this case series could increase the risk of cryptococcosis after SARS-CoV-2 infection.

show abstract

“…However, new therapeutic regimens have been shown to decrease the viral load or even to make it undetectable, thus reducing morbidity and mortality. Although ART has been shown to be highly effective and safe, some patients may still progress to immunosuppression and become susceptible to opportunistic infections, such as cryptococcosis [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical and Epidemiological Characteristics of Neurocryptococcosis Associated with HIV in Northeastern Brazil

Oliveira

Sousa

Freitas

et al. 2023

Viruses

View full text Add to dashboard Cite

Cryptococcal meningitis is a serious infection of the central nervous system that is predominant in developing countries, caused by fungi of the genus Cryptococcus, and which affects immunosuppressed patients, especially those with HIV. Here, we aim to diagnose and characterize the clinical–epidemiological profile of cryptococcosis in patients admitted to two tertiary public hospitals in northeastern Brazil. The study is divided into three moments: (1) the isolation of fungus and diagnosis from biological samples collected between 2017 and 2019, (2) a description of the clinical and epidemiological characteristics of the patients, and (3) the experimental tests related to an in vitro susceptibility antifungal profile. The species were identified by MALDI-TOF/MS. Among the 100 patients evaluated, 24 (24.5%) were diagnosed with cryptococcosis based on positive culture. Clinical–epidemiological analysis showed a slightly higher prevalence in men between 30 and 39 years. When comparing the date of HIV diagnosis and the development of cryptococcosis, it was observed that 50% received the diagnosis of infection by cryptococcosis after or equal to a period of 12 months from being diagnosed with HIV; the other 50% received it within the first 30 days of the HIV diagnosis. Neurocryptococcosis was the most prevalent clinical form, and, at the time of hospital admission, the most common clinical signs were high fever (75%), intense headache (62.50%), and neck stiffness (33.33%). The cerebrospinal fluid showed 100% sensitivity and positivity for direct examination by India ink, and fungal culture. The mortality rate in this study was 46% (11/24), a lower rate than in the other literature. An antifungigram showed that 20 (83.33%) isolates were susceptible to amphotericin B and 15 (62.5%) to fluconazole. Mass spectrometry identified 100% of the isolates as Cryptococcus neoformans. In Brazil, this infection is not mandatory notifiable. Therefore, although there is little information on the subject, it is obsolete and does not express the reality of the facts, mainly in the northeast region, where this information is insufficient. The data obtained in this research contribute to the epidemiological knowledge of this mycosis in Brazil and will serve as a basis for future globally comparative epidemiological studies.

show abstract

Cryptococcus neoformans Infection in the Central Nervous System: The Battle between Host and Pathogen

Cited by 39 publications

References 220 publications

Fungi activate Toll-1 dependent immune evasion to induce cell loss in the host brain

Fungi activate Toll-1 dependent immune evasion to induce cell loss in the host brain

Cerebral Cryptococcosis Associated with CD4+ T-lymphocytopenia in Non-HIV Patients after SARS-CoV-2 Infection: Case Series in a Specialized Institute in Lima, Peru

Clinical and Epidemiological Characteristics of Neurocryptococcosis Associated with HIV in Northeastern Brazil

Contact Info

Product

Resources

About