Phagocytosis of<i>Cryptococcus neoformans</i>by, and Nonlytic Exocytosis from,<i>Acanthamoeba castellanii</i>

Chrisman, Cara J.; Alvarez, Mauricio; Casadevall, Arturo

doi:10.1128/aem.00812-10

Cited by 69 publications

(63 citation statements)

References 37 publications

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“…12,13,54,56 Similar phenomena have been described also in other non-mammalian hosts, such as amoebas and hemocytes from Drosophila melanogaster. 20,57,58 These results enforce the hypothesis that the intracellular pathogenesis is a virulence trait that C. neoformans has acquired after environmental interactions, 21 and allows the yeast to escape from death by macrophages in more complex hosts. Some entomopathogenic fungi, such as Metarhizium anisopliae or Beauveria bassiana, can also affect the phagocytic activity Figure 4.…”

Section: Discussionsupporting

confidence: 72%

Cryptococcus neoformansinduces antimicrobial responses and behaves as a facultative intracellular pathogen in the non mammalian modelGalleria mellonella

et al. 2014

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Section: Discussionsupporting

confidence: 72%

Cryptococcus neoformansinduces antimicrobial responses and behaves as a facultative intracellular pathogen in the non mammalian modelGalleria mellonella

et al. 2014

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“…Nonlytic exocytosis has been observed in murine (12), human (19), and insect (20) cells, which would suggest that this process is a conserved mechanism for exiting phagocytic cells. The fact that nonlytic exocytosis of C. neoformans also occurs in amoeba is consistent with the idea that many aspects of cryptococcal intracellular pathogenesis were selected by interactions with protozoan predators encountered in the environment (21). Despite considerable progress since nonlytic exocytosis was independently described by two groups in 2006 (11,12), many details of this process remain unknown.…”

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confidence: 53%

Temporal Kinetics and Quantitative Analysis of Cryptococcus neoformans Nonlytic Exocytosis

2014

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Cryptococcus neoformans is a facultative intracellular pathogen and the causative agent of cryptococcosis, a disease that is often fatal to those with compromised immune systems. C. neoformans has the capacity to escape phagocytic cells through a process known as nonlytic exocytosis whereby the cryptococcal cell is released from the macrophage into the extracellular environment, leaving both the host and pathogen alive. Little is known about the mechanism behind nonlytic exocytosis, but there is evidence that both the fungal and host cells contribute to the process. In this study, we used time-lapse movies of C. neoformans-infected macrophages to delineate the kinetics and quantitative aspects of nonlytic exocytosis. We analyzed approximately 800 macrophages containing intracellular C. neoformans and identified 163 nonlytic exocytosis events that were further characterized into three subcategories: type I (complete emptying of macrophage), type II (partial emptying of macrophage), and type III (cell-tocell transfer). The majority of type I and II events occurred after several hours of intracellular residence, whereas type III events occurred significantly (P < 0.001) earlier in the course of macrophage infection. Our results show that nonlytic exocytosis is a morphologically and temporally diverse process that occurs relatively rapidly in the course of macrophage infection.

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“…5A; see Movie S5 in the supplemental material). This is reminiscent of the exocytic process previously observed in cryptococcal infections in vitro (48,49,59) and in vivo in mice (60). Although many of the yeast cells adhered to nearby macrophages after release, a subset of them entered the bloodstream.…”

Section: Resultsmentioning

confidence: 93%

A Zebrafish Model of Cryptococcal Infection Reveals Roles for Macrophages, Endothelial Cells, and Neutrophils in the Establishment and Control of Sustained Fungemia

et al. 2016

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Cryptococcal meningoencephalitis is a fungal infection that predominantly affects immunocompromised patients and is uniformly fatal if left untreated. Timely diagnosis is difficult, and screening or prophylactic measures have generally not been successful. Thus, we need a better understanding of early, asymptomatic pathogenesis. Inhaled cryptococci must survive the host immune response, escape the lung, and persist within the bloodstream in order to reach and invade the brain. Here we took advantage of the zebrafish larval infection model to assess the process of cryptococcal infection and disease development sequentially in a single host. Using yeast or spores as infecting particles, we discovered that both cell types survived and replicated intracellularly and that both ultimately established a sustained, low-level fungemia. We propose that the establishment and maintenance of this sustained fungemia is an important stage of disease progression that has been difficult to study in other model systems. Our data suggest that sustained fungemia resulted from a pattern of repeated escape from, and reuptake by, macrophages, but endothelial cells were also seen to play a role as a niche for cryptococcal survival. Circulating yeast collected preferentially in the brain vasculature and eventually invaded the central nervous system (CNS). As suggested previously in a mouse model, we show here that neutrophils can play a valuable role in limiting the sustained fungemia, which can lead to meningoencephalitis. This early stage of pathogenesis-a balanced interaction between cryptococcal cells, macrophages, endothelial cells, and neutrophils-could represent a window for timely detection and intervention strategies for cryptococcal meningoencephalitis. R ecent data from Uganda and Tanzania indicate that there are over 10,000 cases of HIV-related cryptococcosis per year in these countries alone (1, 2). Of those, roughly 5,000 to 8,000 (54 to 79%) are fatal. At a global scale, the survival rate is similarly poor, and over 600,000 deaths are attributed to Cryptococcus neoformans every year (3). The high mortality rate is in part due to difficulties in timely diagnosis; even in susceptible hosts, clinical signs of the initial pulmonary infection can be subtle or essentially absent (4). Studies in this population using serum cryptococcal antigen testing suggest that antigenemia (which may or may not represent actual fungemia) is a harbinger of meningoencephalitis but can precede it by weeks or more (5, 6). Once the infection has progressed to clinical meningoencephalitis, the prognosis is grim even with aggressive treatment. Beyond the HIV-infected population, a growing transplant and otherwise immunosuppressed population is also vulnerable, and even an immunocompetent host may be susceptible to infection and disease caused by the closely related species Cryptococcus gattii (7). An understanding of the events prior to fulminant disease is critical to better management of patients at risk for cryptococcal meningoencephalitis.While ...

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Phagocytosis ofCryptococcus neoformansby, and Nonlytic Exocytosis from,Acanthamoeba castellanii

Cited by 69 publications

References 37 publications

Cryptococcus neoformansinduces antimicrobial responses and behaves as a facultative intracellular pathogen in the non mammalian modelGalleria mellonella

Cryptococcus neoformansinduces antimicrobial responses and behaves as a facultative intracellular pathogen in the non mammalian modelGalleria mellonella

Temporal Kinetics and Quantitative Analysis of Cryptococcus neoformans Nonlytic Exocytosis

A Zebrafish Model of Cryptococcal Infection Reveals Roles for Macrophages, Endothelial Cells, and Neutrophils in the Establishment and Control of Sustained Fungemia

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