An intracellular arrangement of Histoplasma capsulatum yeast-aggregates generates nuclear damage to the cultured murine alveolar macrophages

Histoplasma capsulatum is responsible for a human systemic mycosis that primarily affects lung tissue. Macrophages are the major effector cells in humans that respond to the fungus, and the development of respiratory disease depends on the ability of Histoplasma yeast cells to survive and replicate...

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Main Authors: Nayla De Souza Pitangui, Janaina De Cássia Orlandi Sardi, Aline Raquel eVoltan, Claudia Tavares edos Santos, Julhiany De Fátima Da Silva, Rosângela Aparecida Moraes da Silva, Felipe Oliveira Souza, Christiane Pienna Soares, Gabriela eRodríguez-Arellanes, Maria Lúcia Taylor, Maria José Soares Mendes-Giannini, Ana Marisa eFusco-Almeida
Format: Article
Language:English
Published: Frontiers Media S.A. 2016-01-01
Series:Frontiers in Microbiology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.01526/full
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author Nayla De Souza Pitangui
Janaina De Cássia Orlandi Sardi
Aline Raquel eVoltan
Claudia Tavares edos Santos
Julhiany De Fátima Da Silva
Rosângela Aparecida Moraes da Silva
Felipe Oliveira Souza
Christiane Pienna Soares
Gabriela eRodríguez-Arellanes
Maria Lúcia Taylor
Maria José Soares Mendes-Giannini
Ana Marisa eFusco-Almeida
author_facet Nayla De Souza Pitangui
Janaina De Cássia Orlandi Sardi
Aline Raquel eVoltan
Claudia Tavares edos Santos
Julhiany De Fátima Da Silva
Rosângela Aparecida Moraes da Silva
Felipe Oliveira Souza
Christiane Pienna Soares
Gabriela eRodríguez-Arellanes
Maria Lúcia Taylor
Maria José Soares Mendes-Giannini
Ana Marisa eFusco-Almeida
author_sort Nayla De Souza Pitangui
collection DOAJ
description Histoplasma capsulatum is responsible for a human systemic mycosis that primarily affects lung tissue. Macrophages are the major effector cells in humans that respond to the fungus, and the development of respiratory disease depends on the ability of Histoplasma yeast cells to survive and replicate within alveolar macrophages. Therefore, the interaction between macrophages and H. capsulatum is a decisive step in the yeast dissemination into host tissues. Although the role played by components of cell-mediated immunity in the host's defense system and the mechanisms used by the pathogen to evade the host immune response are well understood, knowledge regarding the effects induced by H. capsulatum in host cells at the nuclear level is limited. According to the present findings, H. capsulatum yeast cells display a unique architectural arrangement during the intracellular infection of cultured murine alveolar macrophages, characterized as a formation of aggregates that seem to surround the host cell nucleus, resembling a crown. This extranuclear organization of yeast-aggregates generates damage on the nucleus of the host cell, producing DNA fragmentation and inducing apoptosis, even though the yeast cells are not located inside the nucleus and do not trigger changes in nuclear proteins. The current study highlights a singular intracellular arrangement of H. capsulatum yeast near to the nucleus of infected murine alveolar macrophages that may contribute to the yeast’s persistence under intracellular conditions, since this fungal pathogen may display different strategies to prevent elimination by the host's phagocytic mechanisms.
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spelling doaj.art-bbd8b3641b2b40ef8fd15682eb0dac1f2022-12-21T18:47:44ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2016-01-01610.3389/fmicb.2015.01526167413An intracellular arrangement of Histoplasma capsulatum yeast-aggregates generates nuclear damage to the cultured murine alveolar macrophagesNayla De Souza Pitangui0Janaina De Cássia Orlandi Sardi1Aline Raquel eVoltan2Claudia Tavares edos Santos3Julhiany De Fátima Da Silva4Rosângela Aparecida Moraes da Silva5Felipe Oliveira Souza6Christiane Pienna Soares7Gabriela eRodríguez-Arellanes8Maria Lúcia Taylor9Maria José Soares Mendes-Giannini10Ana Marisa eFusco-Almeida11UNESP - Univ Estadual Paulista, Departamento de Análises Clínicas, Faculdade de Ciências FarmacêuticasUNESP - Univ Estadual Paulista, Departamento de Análises Clínicas, Faculdade de Ciências FarmacêuticasUNESP - Univ Estadual Paulista, Departamento de Análises Clínicas, Faculdade de Ciências FarmacêuticasUNESP - Univ Estadual Paulista, Departamento de Análises Clínicas, Faculdade de Ciências FarmacêuticasUNESP - Univ Estadual Paulista, Departamento de Análises Clínicas, Faculdade de Ciências FarmacêuticasUNESP - Univ Estadual Paulista, Departamento de Análises Clínicas, Faculdade de Ciências FarmacêuticasUNESP - Univ Estadual Paulista, Departamento de Análises Clínicas, Faculdade de Ciências FarmacêuticasUNESP - Univ Estadual Paulista, Departamento de Análises Clínicas, Faculdade de Ciências FarmacêuticasUNAM - Universidad Nacional Autónoma de México, Departamento de Microbiologia y Parasitologia, Facultad de MedicinaUNAM - Universidad Nacional Autónoma de México, Departamento de Microbiologia y Parasitologia, Facultad de MedicinaUNESP - Univ Estadual Paulista, Departamento de Análises Clínicas, Faculdade de Ciências FarmacêuticasUNESP - Univ Estadual Paulista, Departamento de Análises Clínicas, Faculdade de Ciências FarmacêuticasHistoplasma capsulatum is responsible for a human systemic mycosis that primarily affects lung tissue. Macrophages are the major effector cells in humans that respond to the fungus, and the development of respiratory disease depends on the ability of Histoplasma yeast cells to survive and replicate within alveolar macrophages. Therefore, the interaction between macrophages and H. capsulatum is a decisive step in the yeast dissemination into host tissues. Although the role played by components of cell-mediated immunity in the host's defense system and the mechanisms used by the pathogen to evade the host immune response are well understood, knowledge regarding the effects induced by H. capsulatum in host cells at the nuclear level is limited. According to the present findings, H. capsulatum yeast cells display a unique architectural arrangement during the intracellular infection of cultured murine alveolar macrophages, characterized as a formation of aggregates that seem to surround the host cell nucleus, resembling a crown. This extranuclear organization of yeast-aggregates generates damage on the nucleus of the host cell, producing DNA fragmentation and inducing apoptosis, even though the yeast cells are not located inside the nucleus and do not trigger changes in nuclear proteins. The current study highlights a singular intracellular arrangement of H. capsulatum yeast near to the nucleus of infected murine alveolar macrophages that may contribute to the yeast’s persistence under intracellular conditions, since this fungal pathogen may display different strategies to prevent elimination by the host's phagocytic mechanisms.http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.01526/fullHost-Pathogen InteractionsHistoplasma capsulatumnucleusalveolar macrophagesintracellular arrangement
spellingShingle Nayla De Souza Pitangui
Janaina De Cássia Orlandi Sardi
Aline Raquel eVoltan
Claudia Tavares edos Santos
Julhiany De Fátima Da Silva
Rosângela Aparecida Moraes da Silva
Felipe Oliveira Souza
Christiane Pienna Soares
Gabriela eRodríguez-Arellanes
Maria Lúcia Taylor
Maria José Soares Mendes-Giannini
Ana Marisa eFusco-Almeida
An intracellular arrangement of Histoplasma capsulatum yeast-aggregates generates nuclear damage to the cultured murine alveolar macrophages
Frontiers in Microbiology
Host-Pathogen Interactions
Histoplasma capsulatum
nucleus
alveolar macrophages
intracellular arrangement
title An intracellular arrangement of Histoplasma capsulatum yeast-aggregates generates nuclear damage to the cultured murine alveolar macrophages
title_full An intracellular arrangement of Histoplasma capsulatum yeast-aggregates generates nuclear damage to the cultured murine alveolar macrophages
title_fullStr An intracellular arrangement of Histoplasma capsulatum yeast-aggregates generates nuclear damage to the cultured murine alveolar macrophages
title_full_unstemmed An intracellular arrangement of Histoplasma capsulatum yeast-aggregates generates nuclear damage to the cultured murine alveolar macrophages
title_short An intracellular arrangement of Histoplasma capsulatum yeast-aggregates generates nuclear damage to the cultured murine alveolar macrophages
title_sort intracellular arrangement of histoplasma capsulatum yeast aggregates generates nuclear damage to the cultured murine alveolar macrophages
topic Host-Pathogen Interactions
Histoplasma capsulatum
nucleus
alveolar macrophages
intracellular arrangement
url http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.01526/full
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