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Successful control of C. neoformans infection is dependent on host macrophages, but macrophages display little ability to kill C. neoformans in vitro. Recently, we reported that ingestion of C. neoformans by mouse macrophages induces early cell cycle progression followed by mitotic arrest, an event that almost certainly reflects host cell damage. The goal of the present work was to understand macrophage pathways affected by C. neoformans toxicity. Infection of macrophages by C. neoformans was associated with alterations in protein translation rate and activation of several stress pathways, such as hypoxia-inducing factor-1-\u03b1, receptor-interacting protein 1, and apoptosis-inducing factor. Concomitantly we observed mitochondrial depolarization in infected macrophages, an observation that was replicated in vivo. We also observed differences in the stress pathways activated, depending on macrophage cell type, consistent with the nonspecific nature of C. neoformans virulence known to infect phylogenetically distant hosts. Our results indicate that C. neoformans infection impairs multiple host cellular functions and undermines the health of these critical phagocytic cells, which can potentially interfere with their ability to clear this fungal pathogen.<\/jats:p>","DOI":"10.4049\/jimmunol.1402350","type":"journal-article","created":{"date-parts":[[2015,2,3]],"date-time":"2015-02-03T06:02:13Z","timestamp":1422943333000},"page":"2345-2357","source":"Crossref","is-referenced-by-count":45,"title":["Macrophage Mitochondrial and Stress Response to Ingestion of <i>Cryptococcus neoformans<\/i>"],"prefix":"10.1093","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7523-3031","authenticated-orcid":false,"given":"Carolina","family":"Coelho","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine of Yeshiva University , Bronx, NY 10461"},{"name":"Centre for Neuroscience and Cell Biology, University of Coimbra , 3004-504 Coimbra ,","place":["Portugal"]},{"name":"Faculty of Medicine, University of Coimbra , 3004-504 Coimbra ,","place":["Portugal"]}]},{"given":"Ana Camila Oliveira","family":"Souza","sequence":"additional","affiliation":[{"name":"Cell Biology Department, Biology Science Institute, University of Brasilia , Brasilia CEP 70910-900 ,","place":["Brazil"]}]},{"given":"Lorena da Silveira","family":"Derengowski","sequence":"additional","affiliation":[{"name":"Cell Biology Department, Biology Science Institute, University of Brasilia , Brasilia CEP 70910-900 ,","place":["Brazil"]}]},{"given":"Carlos","family":"de Leon-Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine of Yeshiva University , Bronx, NY 10461"}]},{"given":"Bo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine of Yeshiva University , Bronx, NY 10461"},{"name":"MD Program, Albert Einstein College of Medicine of Yeshiva University , Bronx, NY 10461"}]},{"given":"Rosiris","family":"Leon-Rivera","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Puerto Rico , R\u00edo Piedras Campus, San Juan ,","place":["Puerto Rico 00931"]},{"name":"Undergraduate Research Program, Albert Einstein College of Medicine of Yeshiva University , Bronx, NY 10461"}]},{"given":"Anamelia Lorenzetti","family":"Bocca","sequence":"additional","affiliation":[{"name":"Cell Biology Department, Biology Science Institute, University of Brasilia , Brasilia CEP 70910-900 ,","place":["Brazil"]}]},{"given":"Teresa","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience and Cell Biology, University of Coimbra , 3004-504 Coimbra ,","place":["Portugal"]},{"name":"Faculty of Medicine, University of Coimbra , 3004-504 Coimbra ,","place":["Portugal"]}]},{"given":"Arturo","family":"Casadevall","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine of Yeshiva University , Bronx, NY 10461"}]}],"member":"286","published-online":{"date-parts":[[2015,3,1]]},"reference":[{"key":"2025030705162586500_r1","doi-asserted-by":"crossref","first-page":"3165","DOI":"10.1073\/pnas.052702799","article-title":"Replication of Cryptococcus neoformans in macrophages is accompanied by phagosomal permeabilization and accumulation of vesicles containing polysaccharide in the cytoplasm","volume":"99","author":"Tucker","year":"2002","journal-title":"Proc. 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