New Perspectives on Cryptococcus and Cryptococcosis

A special issue of Journal of Fungi (ISSN 2309-608X).

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 3086

Special Issue Editor


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Guest Editor
Departamento de Biologia Molecular e Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Interests: molecular microbiology; fungal pathogens; Cryptococcus; fungal diseases

Special Issue Information

Dear Colleagues,

Fungal infections are an emergent worldwide public health concern. Recently, the World Health Organization (WHO) published the Fungal priority pathogens list to guide research, development, and public health action. The human pathogen Cryptococcus neoformans was listed in the critical priority group, which highlights the global impact of cryptococcosis. This infectious disease affects predominantly immunocompromised patients, and causes 180,000 deaths each year. Cryptococcosis is acquired after the inhalation of yeast propagules that can disseminate to the central nervous system, leading to cryptococcal meningitis. Once inside the host, cryptococcal cells undergo a variety of adaptative processes that are mainly regulated by transcription factors and signaling pathways. The complete understanding of Cryptococcus biology and cryptococcosis establishment, including the deciphering of virulence and antifungal resistance mechanisms, is crucial to overcoming this important fungal infection. Considering these aspects, the aim of this Special Issue is to contribute new perspectives on Cryptococcus and cryptococcosis through original articles and comprehensive reviews.

Dr. Lívia Kmetzsch
Guest Editor

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Keywords

  • Cryptococcus
  • cryptococcosis
  • fungal virulence
  • antifungal resistance
  • host–pathogen interactions

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Published Papers (2 papers)

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Research

17 pages, 2909 KiB  
Article
Card9 Broadly Regulates Host Immunity against Experimental Pulmonary Cryptococcus neoformans 52D Infection
by Isabelle Angers, Wided Akik, Annie Beauchamp, Irah L. King, Larry C. Lands and Salman T. Qureshi
J. Fungi 2024, 10(6), 434; https://doi.org/10.3390/jof10060434 - 19 Jun 2024
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Abstract
The ubiquitous soil-associated fungus Cryptococcus neoformans causes pneumonia that may progress to fatal meningitis. Recognition of fungal cell walls by C-type lectin receptors (CLRs) has been shown to trigger the host immune response. Caspase recruitment domain-containing protein 9 (Card9) is an intracellular adaptor [...] Read more.
The ubiquitous soil-associated fungus Cryptococcus neoformans causes pneumonia that may progress to fatal meningitis. Recognition of fungal cell walls by C-type lectin receptors (CLRs) has been shown to trigger the host immune response. Caspase recruitment domain-containing protein 9 (Card9) is an intracellular adaptor that is downstream of several CLRs. Experimental studies have implicated Card9 in host resistance against C. neoformans; however, the mechanisms that are associated with susceptibility to progressive infection are not well defined. To further characterize the role of Card9 in cryptococcal infection, Card9em1Sq mutant mice that lack exon 2 of the Card9 gene on the Balb/c genetic background were created using CRISPR-Cas9 genome editing technology and intratracheally infected with C. neoformans 52D. Card9em1Sq mice had significantly higher lung and brain fungal burdens and shorter survival after C. neoformans 52D infection. Susceptibility of Card9em1Sq mice was associated with lower pulmonary cytokine and chemokine production, as well as reduced numbers of CD4+ lymphocytes, neutrophils, monocytes, and dendritic cells in the lungs. Histological analysis and intracellular cytokine staining of CD4+ T cells demonstrated a Th2 pattern of immunity in Card9em1Sq mice. These findings demonstrate that Card9 broadly regulates the host inflammatory and immune response to experimental pulmonary infection with a moderately virulent strain of C. neoformans. Full article
(This article belongs to the Special Issue New Perspectives on Cryptococcus and Cryptococcosis)
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16 pages, 3879 KiB  
Article
Host–Pathogen Interactions and Correlated Factors That Are Affected in Replicative-Aged Cryptococcus neoformans
by Vanessa K. A. Silva, Sungyun Min, Kyungyoon Yoo and Bettina C. Fries
J. Fungi 2024, 10(4), 279; https://doi.org/10.3390/jof10040279 - 10 Apr 2024
Viewed by 1518
Abstract
Cryptococcus neoformans is a facultative intracellular fungal pathogen. Ten-generation-old (10GEN) C. neoformans cells are more resistant to phagocytosis and killing by macrophages than younger daughter cells. However, mechanisms that mediate this resistance and intracellular parasitism are poorly understood. Here, we identified important factors [...] Read more.
Cryptococcus neoformans is a facultative intracellular fungal pathogen. Ten-generation-old (10GEN) C. neoformans cells are more resistant to phagocytosis and killing by macrophages than younger daughter cells. However, mechanisms that mediate this resistance and intracellular parasitism are poorly understood. Here, we identified important factors for the intracellular survival of 10GEN C. neoformans, such as urease activity, capsule synthesis, and DNA content using flow cytometry and fluorescent microscopy techniques. The real-time visualization of time-lapse imaging was applied to determine the phagosomal acidity, membrane permeability, and vomocytosis (non-lytic exocytosis) rate in J774 macrophages that phagocytosed C. neoformans of different generational ages. Our results showed that old C. neoformans exhibited higher urease activity and enhanced Golgi activity. In addition, old C. neoformans were more likely to be arrested in the G2 phase, resulting in the occasional formation of aberrant trimera-like cells. To finish, the advanced generational age of the yeast cells slightly reduced vomocytosis events within host cells, which might be associated with increased phagolysosome pH and membrane permeability. Altogether, our results suggest that old C. neoformans prevail within acidic phagolysosomes and can manipulate the phagosome pH. These strategies may be used by old C. neoformans to resist phagosomal killing and drive cryptococcosis pathogenesis. The comprehension of these essential host–pathogen interactions could further shed light on mechanisms that bring new insights for novel antifungal therapeutic design. Full article
(This article belongs to the Special Issue New Perspectives on Cryptococcus and Cryptococcosis)
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