Cell-to-cell spread and massive vacuole formation after Cryptococcus neoformans infection of murine macrophages

Alvarez, Mauricio; Casadevall, Arturo

doi:10.1186/1471-2172-8-16

Cited by 121 publications

(129 citation statements)

References 17 publications

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“…However, it could also reflect a mechanism developed by the immune system in which macrophages overloaded with yeast cells transfer part of the fungal burden to uninfected or less-infected macrophages. Some of these phenomena (macrophage fusion, yeast extrusion, and transfer between macrophages) have been described in other fungal pathogens (1,2,13,15,16), which suggests that these processes represent a universal strategy developed by the host cells to control the infection independently of the pathogen engulfed.…”

Section: Discussionmentioning

confidence: 95%

The Interaction between Candida krusei and Murine Macrophages Results in Multiple Outcomes, Including Intracellular Survival and Escape from Killing

et al. 2011

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Candida krusei is a fungal pathogen of interest for the scientific community for its intrinsic resistance to fluconazole. Little is known about the interaction of this yeast with host immune cells. In this work, we have characterized the outcome of the interaction between C. krusei and murine macrophages. Once C. krusei was internalized, we observed different phenomena. In a macrophage-like cell line, C. krusei survived in a significant number of macrophages and induced filamentation and macrophage explosion. Phagocytosis of C. krusei led to actin polymerization around the yeast cells at the site of entry. Fluorescent specific staining with anti-Lamp1 and LysoTracker indicated that after fungal internalization, there was a phagolysosome maturation defect, a phenomenon that was more efficient when the macrophages phagocytosed killed yeast cells. Using cell line macrophages, we also observed macrophage fusion after cell division. When we used primary resident peritoneal macrophages in addition to macrophage explosion, we also observed a strong chemotaxis of uninfected macrophages to regions where C. krusei-infected macrophages were present. We also noticed yeast transfer phenomena between infected macrophages. Primary macrophages inhibited pseudohypha elongation more efficiently than the macrophage-like cell line, suggesting that C. krusei infection was better controlled by the former macrophages. Primary macrophages induced more tumor necrosis factor alpha (TNF-␣) and interleukin-6 (IL-6) than the macrophage-like cell line. Our results demonstrate that C. krusei can exploit the macrophages for replication, although other different outcomes are also possible, indicating that the interaction of this pathogen with phagocytic cells is very complex and regulated by multiple factors.

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Section: Discussionmentioning

confidence: 95%

The Interaction between Candida krusei and Murine Macrophages Results in Multiple Outcomes, Including Intracellular Survival and Escape from Killing

et al. 2011

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“…However, whether the actin flashes play a direct role in the Cryptococcus exit mechanism remains to be defined. In addition, a direct cell-tocell spreading mechanism between macrophages without an exposure of the pathogen to the extracellular milieu was proposed, but its details and significance remain unclear (8,91).…”

Section: Exocytosis and Autophagy-related Mechanismsmentioning

confidence: 99%

Prison Break: Pathogens' Strategies To Egress from Host Cells

Friedrich

Hagedorn

Soldati‐Favre

et al. 2012

Microbiol Mol Biol Rev

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SUMMARYA wide spectrum of pathogenic bacteria and protozoa has adapted to an intracellular life-style, which presents several advantages, including accessibility to host cell metabolites and protection from the host immune system. Intracellular pathogens have developed strategies to enter and exit their host cells while optimizing survival and replication, progression through the life cycle, and transmission. Over the last decades, research has focused primarily on entry, while the exit process has suffered from neglect. However, pathogen exit is of fundamental importance because of its intimate association with dissemination, transmission, and inflammation. Hence, to fully understand virulence mechanisms of intracellular pathogens at cellular and systemic levels, it is essential to consider exit mechanisms to be a key step in infection. Exit from the host cell was initially viewed as a passive process, driven mainly by physical stress as a consequence of the explosive replication of the pathogen. It is now recognized as a complex, strategic process termed “egress,” which is just as well orchestrated and temporally defined as entry into the host and relies on a dynamic interplay between host and pathogen factors. This review compares egress strategies of bacteria, pathogenic yeast, and kinetoplastid and apicomplexan parasites. Emphasis is given to recent advances in the biology of egress in mycobacteria and apicomplexans.

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“…Despite this, the opportunistic fungal pathogen Cryptococcus neoformans is able to inhabit and replicate within phagocytes of the mammalian host and to exit these cells unharmed (1,2,40). The intracellular pathogenicity of C. neoformans is most likely facilitated by stress resistance mechanisms, including a number of antioxidant proteins and pathways involved in the detoxification of ROS and RNS.…”

mentioning

confidence: 99%

Isocitrate Dehydrogenase Is Important for Nitrosative Stress Resistance in Cryptococcus neoformans, but Oxidative Stress Resistance Is Not Dependent on Glucose-6-Phosphate Dehydrogenase

et al. 2010

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The opportunistic intracellular fungal pathogen Cryptococcus neoformans depends on many antioxidant and denitrosylating proteins and pathways for virulence in the immunocompromised host. These include the glutathione and thioredoxin pathways, thiol peroxidase, cytochrome c peroxidase, and flavohemoglobin denitrosylase. All of these ultimately depend on NADPH for either catalytic activity or maintenance of a reduced, functional form. The need for NADPH during oxidative stress is well established in many systems, but a role in resistance to nitrosative stress has not been as well characterized. In this study we investigated the roles of two sources of NADPH, glucose-6-phosphate dehydrogenase (Zwf1) and NADP ؉ -dependent isocitrate dehydrogenase (Idp1), in production of NADPH and resistance to oxidative and nitrosative stress. Deletion of ZWF1 in C. neoformans did not result in an oxidative stress sensitivity phenotype or changes in the amount of NADPH produced during oxidative stress compared to those for the wild type. Deletion of IDP1 resulted in greater sensitivity to nitrosative stress than to oxidative stress. The amount of NADPH increased 2-fold over that in the wild type during nitrosative stress, and yet the idp1⌬ strain accumulated more mitochondrial damage than the wild type during nitrosative stress. This is the first report of the importance of Idp1 and NADPH for nitrosative stress resistance.

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Cell-to-cell spread and massive vacuole formation after Cryptococcus neoformans infection of murine macrophages

Cited by 121 publications

References 17 publications

The Interaction between Candida krusei and Murine Macrophages Results in Multiple Outcomes, Including Intracellular Survival and Escape from Killing

The Interaction between Candida krusei and Murine Macrophages Results in Multiple Outcomes, Including Intracellular Survival and Escape from Killing

Prison Break: Pathogens' Strategies To Egress from Host Cells

Isocitrate Dehydrogenase Is Important for Nitrosative Stress Resistance in Cryptococcus neoformans, but Oxidative Stress Resistance Is Not Dependent on Glucose-6-Phosphate Dehydrogenase

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