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Insights into the host-pathogen interaction: C. albicans manipulation of macrophage pyroptosis

The innate immune system is the first defense against invasive fungal infections, including those caused by Candida albicans. Although C. albicans can exist as a commensal, it can also cause systemic or mucosal infections, especially when the innate immune system is impaired. A key aspect of the int...

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Autores principales: O’Meara, Teresa R., Cowen, Leah E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Shared Science Publishers OG 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282020/
https://www.ncbi.nlm.nih.gov/pubmed/30533421
http://dx.doi.org/10.15698/mic2018.12.662
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author O’Meara, Teresa R.
Cowen, Leah E.
author_facet O’Meara, Teresa R.
Cowen, Leah E.
author_sort O’Meara, Teresa R.
collection PubMed
description The innate immune system is the first defense against invasive fungal infections, including those caused by Candida albicans. Although C. albicans can exist as a commensal, it can also cause systemic or mucosal infections, especially when the innate immune system is impaired. A key aspect of the interaction between C. albicans and innate immune cells is the ability of C. albicans to induce macrophage pyroptosis, an inflammatory cell death program. The induction of pyroptosis is temporally coupled to a morphological transition between yeast and filamentous growth. However, the relationship between fungal morphogenesis and activation of macrophage pyroptosis is complex. Although most C. albicans mutants with defects in filamentation are also unable to induce macrophage pyroptosis, filamentation is neither necessary nor sufficient for activation of pyroptosis. In our study [O’Meara et al., 2018 mBio], we set out to map the genetic circuitry in both the fungus and the host macrophage that leads to pyroptosis, and determine the impact of altered pyroptosis on infection. We identified 98 C. albicans genes that were dispensable for filamentation in the macrophage but important for enabling the fungus to activate macrophage pyroptosis. Using these mutants, we demonstrated that pyroptosis is required for robust neutrophil accumulation at the site of C. albicans infection. We also showed that, in contrast to previous work, inflammasome priming and activation can be decoupled in the response to C. albicans infection, and that phagolysosomal rupture is not the inflammasome activating signal. Our work provides the most comprehensive analysis of C. albicans interactions with host cells to date, and reveals new factors governing the outcomes of this interaction.
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spelling pubmed-62820202018-12-07 Insights into the host-pathogen interaction: C. albicans manipulation of macrophage pyroptosis O’Meara, Teresa R. Cowen, Leah E. Microb Cell Microreview The innate immune system is the first defense against invasive fungal infections, including those caused by Candida albicans. Although C. albicans can exist as a commensal, it can also cause systemic or mucosal infections, especially when the innate immune system is impaired. A key aspect of the interaction between C. albicans and innate immune cells is the ability of C. albicans to induce macrophage pyroptosis, an inflammatory cell death program. The induction of pyroptosis is temporally coupled to a morphological transition between yeast and filamentous growth. However, the relationship between fungal morphogenesis and activation of macrophage pyroptosis is complex. Although most C. albicans mutants with defects in filamentation are also unable to induce macrophage pyroptosis, filamentation is neither necessary nor sufficient for activation of pyroptosis. In our study [O’Meara et al., 2018 mBio], we set out to map the genetic circuitry in both the fungus and the host macrophage that leads to pyroptosis, and determine the impact of altered pyroptosis on infection. We identified 98 C. albicans genes that were dispensable for filamentation in the macrophage but important for enabling the fungus to activate macrophage pyroptosis. Using these mutants, we demonstrated that pyroptosis is required for robust neutrophil accumulation at the site of C. albicans infection. We also showed that, in contrast to previous work, inflammasome priming and activation can be decoupled in the response to C. albicans infection, and that phagolysosomal rupture is not the inflammasome activating signal. Our work provides the most comprehensive analysis of C. albicans interactions with host cells to date, and reveals new factors governing the outcomes of this interaction. Shared Science Publishers OG 2018-11-12 /pmc/articles/PMC6282020/ /pubmed/30533421 http://dx.doi.org/10.15698/mic2018.12.662 Text en https://creativecommons.org/licenses/by/4.0/ This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
spellingShingle Microreview
O’Meara, Teresa R.
Cowen, Leah E.
Insights into the host-pathogen interaction: C. albicans manipulation of macrophage pyroptosis
title Insights into the host-pathogen interaction: C. albicans manipulation of macrophage pyroptosis
title_full Insights into the host-pathogen interaction: C. albicans manipulation of macrophage pyroptosis
title_fullStr Insights into the host-pathogen interaction: C. albicans manipulation of macrophage pyroptosis
title_full_unstemmed Insights into the host-pathogen interaction: C. albicans manipulation of macrophage pyroptosis
title_short Insights into the host-pathogen interaction: C. albicans manipulation of macrophage pyroptosis
title_sort insights into the host-pathogen interaction: c. albicans manipulation of macrophage pyroptosis
topic Microreview
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282020/
https://www.ncbi.nlm.nih.gov/pubmed/30533421
http://dx.doi.org/10.15698/mic2018.12.662
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