Identification of App1 as a regulator of phagocytosis and virulence of Cryptococcus neoformans

Luberto, Chiara; Martinez-Mariño, Beatriz; Taraskiewicz, Daniel; Bolaños, Benjamin; Chitano, Pasquale; Toffaletti, Dena L.; Cox, Gary M.; Perfect, John R.; Hannun, Yusuf A.; Balish, Edward; Poeta, Maurizio Del

doi:10.1172/jci18309

Cited by 144 publications

(110 citation statements)

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“…The presence of significant mannoprotein fractions in the cell walls could also explain the presence of xylose as previous studies showed that C. neoformans mannoproteins might contain xylose and xylose-phosphate structures (Reilly et al, 2011; Park et al, 2012). Some mannoproteins are recognized as primary cryptococcal antigens (Murphy et al, 1988; Levitz et al, 2001; Mansour et al, 2002), while other mannoproteins such as MP4 and App1 dampen the host immune response against C. neoformans (Coenjaerts et al, 2001; Luberto et al, 2003). During infection, titan cells confer protection from phagocytosis to the entire cryptococcal population (Crabtree et al, 2012; Okagaki and Nielsen, 2012).…”

Section: Discussionmentioning

confidence: 99%

Titan cell production in Cryptococcus neoformans reshapes the cell wall and capsule composition during infection

et al. 2018

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Cryptococcus neoformans is a human fungal pathogen that often causes infections in immunocompromised individuals. Upon inhalation into the lungs C. neoformans differentiates into cells with altered size and morphology, including production of large titan cells. Titan cells possess thickened cell wall and dense, cross-linked capsule when compared to in vitro grown cells. In addition, titan cells have increased cell wall chitin that is associated with a detrimental anti-inflammatory immune response. Here we examined the cell wall and capsule composition of in vitro, in vivo typical-sized and in vivo titan cells using High Performance Liquid Chromatography (HPLC). The monomer composition of cell wall polysaccharides showed that in vivo C. neoformans cells contained more glucosamine and less glucose than in vitro cells, suggesting alteration in abundance of both chitin and glucans, respectively. Low levels of galactosamine were also detected in carbohydrates from both in vivo and vitro cells. Within the in vivo cell population, differences in the proportions of cell wall and capsule monomers between typical and titan cells were also observed. Taken together, these results demonstrate that C. neoformans reshapes its cell wall and capsule composition during infection. These cell wall and capsule alterations likely help C. neoformans escape recognition by, and allow modulation of, the host immune system.

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Section: Discussionmentioning

confidence: 99%

Titan cell production in Cryptococcus neoformans reshapes the cell wall and capsule composition during infection

et al. 2018

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“…In a murine model, alveolar macrophages could rapidly phagocytose yeast cells after the intratracheal infection [46]. However, yeast cells of some strains can adopt different strategies to avoid phagocytosis [62,63]. …”

Section: Discussionmentioning

confidence: 99%

Morphology and its underlying genetic regulation impact the interaction between Cryptococcus neoformans and its hosts

2015

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Cryptococcus neoformans is a fungus that causes the majority of fatal cryptococcal meningitis cases worldwide. This pathogen is capable of assuming different morphotypes: yeast, pseudohypha, and hypha. The yeast form is the most common cell type observed clinically. The hyphal and pseudohyphal forms are rarely observed in the clinical setting and are considered attenuated in virulence. However, as a ubiquitous environmental pathogen, Cryptococcus interacts with various organisms, and it is known to be parasitic to different hosts. Capitalizing on recent discoveries, morphogenesis regulators were manipulated to examine the impact of cell shape on the cryptococcal interaction with three different host systems: the soil amoeba Acanthamoeba castellanii (a protist), the greater wax moth Galleria mellonella (an insect), and the murine macrophage cell line J774A.1 (mammalian cells). The regulation of Ace2 and morphogenesis (RAM) pathway is a highly conserved pathway among eukaryotes that regulates cytokinesis. Disruption of any of five RAM components in Cryptococcus renders cells constitutively in the pseudohyphal form. The transcription factor Znf2 is the master activator of the yeast to hyphal transition. Deletion of ZNF2 locks cells in the yeast form, while overexpression of this regulator drives hyphal growth. Genetic epistasis analyses indicate that the RAM and the Znf2 pathways regulate distinct aspects of cryptococcal morphogenesis and independently of each other. These investigations using the Cryptococcus RAM and ZNF2 mutants indicate that cell shape, cell size, and likely cell surface properties weigh differently on the outcome of cryptococcal interactions with different hosts. Thus, certain traits evolved in Cryptococcus that are beneficial within one host might be detrimental when a different host is encountered.

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“…C. neoformans, C. albicans , and A. fumigatus conidia can inhibit complement activity by secreting a small protein or binding several complement regulatory factors (Luberto et al, 2003; Meri et al, 2004; Behnsen et al, 2008). Additionally, the terminal MAC of the complement system is not capable of lysing the fungal cell wall (Kozel, 1996).…”

Section: Controlmentioning

confidence: 99%

Anti-Immune Strategies of Pathogenic Fungi

Marcos¹,

Oliveira²,

Melo³

et al. 2016

Front. Cell. Infect. Microbiol.

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Pathogenic fungi have developed many strategies to evade the host immune system. Multiple escape mechanisms appear to function together to inhibit attack by the various stages of both the adaptive and the innate immune response. Thus, after entering the host, such pathogens fight to overcome the immune system to allow their survival, colonization and spread to different sites of infection. Consequently, the establishment of a successful infectious process is closely related to the ability of the pathogen to modulate attack by the immune system. Most strategies employed to subvert or exploit the immune system are shared among different species of fungi. In this review, we summarize the main strategies employed for immune evasion by some of the major pathogenic fungi.

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Identification of App1 as a regulator of phagocytosis and virulence of Cryptococcus neoformans

Cited by 144 publications

References 49 publications

Titan cell production in Cryptococcus neoformans reshapes the cell wall and capsule composition during infection

Titan cell production in Cryptococcus neoformans reshapes the cell wall and capsule composition during infection

Morphology and its underlying genetic regulation impact the interaction between Cryptococcus neoformans and its hosts

Anti-Immune Strategies of Pathogenic Fungi

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