Vomocytosis: What we know so far

Seoane, Paula I.; May, Robin C.

doi:10.1111/cmi.13145

Cited by 29 publications

(33 citation statements)

References 38 publications

(73 reference statements)

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“…A 2018 paper showed that D. discoideum phagocytosed C. neoformans but was unable to kill the yeast, a phenomenon similar to macrophages. However, Watkins et al were able to ascertain that C. neoformans can either be expelled from the amoeba, or when the amoeba is pharmacologically blocked, C. neoformans can escape in a non-lytic manner ( 68 ), a recent phenomenon termed vomocytosis ( 69 , 70 ). Ultimately, the amoeba model represents a novel approach for future studies on the cellular level, which has implications to how macrophages interact with C. neoformans in the host.…”

Section: Animal Models For Studying Cryptococcosismentioning

confidence: 99%

“…Because C. neoformans can survive and replicate within macrophages ( 13 , 156 , 157 ), M2 macrophages that have little to no fungicidal activity can harbor large numbers of yeast cells leading to dysfunctional macrophages ( 69 , 145 ). Through either lytic or non-lytic (termed vomocytosis) exocytosis, cryptococcal cells may exit the macrophages either in the lungs or elsewhere if the macrophages have also left the lungs ( 70 , 146 , 158 ). This ability of C. neoformans to “hide” within macrophages protects the yeast against the harsh extracellular environment containing antimicrobial peptides and complement as well as killing by neutrophils, NK cells, and T cells ( 75 ).…”

Section: Modeling Cryptococcal Infections and What Has Been Learnedmentioning

confidence: 99%

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Animal Models of Cryptococcus neoformans in Identifying Immune Parameters Associated With Primary Infection and Reactivation of Latent Infection

2020

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Cryptococcus species are environmental fungal pathogens and the causative agents of cryptococcosis. Infection occurs upon inhalation of infectious particles, which proliferate in the lung causing a primary infection. From this primary lung infection, fungal cells can eventually disseminate to other organs, particularly the brain, causing lethal meningoencephalitis. However, in most cases, the primary infection resolves with the formation of a lung granuloma. Upon severe immunodeficiency, dormant cryptococcal cells will start proliferating in the lung granuloma and eventually will disseminate to the brain. Many investigators have sought to study the protective host immune response to this pathogen in search of host parameters that keep the proliferation of cryptococcal cells under control. The majority of the work assimilates research carried out using the primary infection animal model, mainly because a reactivation model has been available only very recently. This review will focus on anti-cryptococcal immunity in both the primary and reactivation models. An understanding of the differences in host immunity between the primary and reactivation models will help to define the key host parameters that control the infections and are important for the research and development of new therapeutic and vaccine strategies against cryptococcosis.

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Section: Animal Models For Studying Cryptococcosismentioning

confidence: 99%

Section: Modeling Cryptococcal Infections and What Has Been Learnedmentioning

confidence: 99%

Animal Models of Cryptococcus neoformans in Identifying Immune Parameters Associated With Primary Infection and Reactivation of Latent Infection

2020

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“…7A and B). High IPR are related to vomocytosis, a mechanism of phagocytic escape commonly used by Cryptococcus (33,34). We therefore determined the vomocytosis levels after exposure of infected macrophages to fenbendazole.…”

Section: Figmentioning

confidence: 99%

Fenbendazole Controls In Vitro Growth, Virulence Potential, and Animal Infection in the Cryptococcus Model

Oliveira

Joffe

Simon

et al. 2020

Antimicrob Agents Chemother

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The human diseases caused by the fungal pathogens Cryptococcus neoformans and Cryptococcus gattii are associated with high indices of mortality and toxic and/or cost-prohibitive therapeutic protocols. The need for affordable antifungals to combat cryptococcal disease is unquestionable. Previous studies suggested benzimidazoles as promising anticryptococcal agents combining low cost and high antifungal efficacy, but their therapeutic potential has not been demonstrated so far. In this study, we investigated the antifungal potential of fenbendazole, the most effective anticryptococcal benzimidazole. Fenbendazole was inhibitory against 17 different isolates of C. neoformans and C. gattii at a low concentration. The mechanism of anticryptococcal activity of fenbendazole involved microtubule disorganization, as previously described for human parasites. In combination with fenbendazole, the concentrations of the standard antifungal amphotericin B required to control cryptococcal growth were lower than those required when this antifungal was used alone. Fenbendazole was not toxic to mammalian cells. During macrophage infection, the anticryptococcal effects of fenbendazole included inhibition of intracellular proliferation rates and reduced phagocytic escape through vomocytosis. Fenbendazole deeply affected the cryptococcal capsule. In a mouse model of cryptococcosis, the efficacy of fenbendazole to control animal mortality was similar to that observed for amphotericin B. These results indicate that fenbendazole is a promising candidate for the future development of an efficient and affordable therapeutic tool to combat cryptococcosis.

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“…In both species, exposure of infected macrophages to fenbendazole resulted in reduced IPR at both inhibitory and sub inhibitory concentrations (Figures 6A and 6B). High IPR are related to vomocytosis, a mechanism of phagocytic scape commonly used by Cryptococcus (28, 29). We therefore determined the vomocytosis levels after exposure of infected macrophages to fenbendazole.…”

Section: Resultsmentioning

confidence: 99%

Fenbendazole controlsin vitrogrowth, virulence potential and animal infection in theCryptococcusmodel

Oliveira

Joffe

Simon

et al. 2020

Preprint

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AbstractThe human diseases caused by the fungal pathogens Cryptococcus neoformans and C. gattii are associated with high indices of mortality, and toxic and/or cost-prohibitive therapeutic protocols. The need for affordable antifungals to combat cryptococcal disease is unquestionable. Previous studies suggested benzimidazoles as promising anti-cryptococcal agents combining low cost and high antifungal efficacy, but their therapeutic potential has not been demonstrated so far. In this study, we investigated the antifungal potential of fenbendazole, the most effective anti-cryptococcal benzimidazole. Fenbendazole was inhibitory against 30 different isolates of C. neoformans and C. gattii at a low concentration. The mechanism of anti-cryptococcal activity of fenbendazole involved microtubule disorganization, as previously described for human parasites. In combination with fenbendazole, the concentrations of the standard antifungal amphotericin B required to control cryptococcal growth were lower than those required when this antifungal was used alone. Fenbendazole was not toxic to mammalian cells. During macrophage infection, the anti-cryptococcal effects of fenbendazole included inhibition of intracellular proliferation rates and reduced phagocytic escape through vomocytosis. Fenbendazole deeply affected the cryptococcal capsule. In a mice model of cryptococcosis, the efficacy of fenbendazole to control animal mortality was similar to that observed for amphotericin B. These results indicate that fenbendazole is a promising candidate for the future development of an efficient and affordable therapeutic tool to combat cryptococcosis.

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Vomocytosis: What we know so far

Cited by 29 publications

References 38 publications

Animal Models of Cryptococcus neoformans in Identifying Immune Parameters Associated With Primary Infection and Reactivation of Latent Infection

Animal Models of Cryptococcus neoformans in Identifying Immune Parameters Associated With Primary Infection and Reactivation of Latent Infection

Fenbendazole Controls In Vitro Growth, Virulence Potential, and Animal Infection in the Cryptococcus Model

Fenbendazole controlsin vitrogrowth, virulence potential and animal infection in theCryptococcusmodel

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