NDLI: The unappreciated intracellular lifestyle of Blastomyces dermatitidis.

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The unappreciated intracellular lifestyle of Blastomyces dermatitidis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Mettelman, Robert Sterkel, Alana K. Wüthrich, Marcel Klein, Bruce S.
Description	Author Affiliation: Sterkel AK ( Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792); Mettelman R ( Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792); Wüthrich M ( Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792); Klein BS ( Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792)
Abstract	Blastomyces dermatitidis, a dimorphic fungus and the causative agent of blastomycosis, is widely considered an extracellular pathogen, with little evidence for a facultative intracellular lifestyle. We infected mice with spores, that is, the infectious particle, via the pulmonary route and studied intracellular residence, transition to pathogenic yeast, and replication inside lung cells. Nearly 80% of spores were inside cells at 24 h postinfection with 10(4) spores. Most spores were located inside of alveolar macrophages, with smaller numbers in neutrophils and dendritic cells. Real-time imaging showed rapid uptake of spores into alveolar macrophages, conversion to yeast, and intracellular multiplication during in vitro coculture. The finding of multiple yeast in a macrophage was chiefly due to intracellular replication rather than multiple phagocytic events or fusion of macrophages. Depletion of alveolar macrophages curtailed infection in mice infected with spores and led to a 26-fold reduction in lung CFU by 6 d postinfection versus nondepleted mice. Phase transition of the spores to yeast was delayed in these depleted mice over a time frame that correlated with reduced lung CFU. Spores cultured in vitro converted to yeast faster in the presence of macrophages than in medium alone. Thus, although advanced B. dermatitidis infection may exhibit extracellular residence in tissue, early lung infection with infectious spores reveals its unappreciated facultative intracellular lifestyle.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1303089
Journal	The Journal of Immunology
Issue Number	4
Volume Number	194
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2015-02-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Blastomyces Physiology Blastomycosis Microbiology Macrophages, Alveolar Animals Disease Models, Animal Mice Mice, Inbred C57bl Neutrophils Spores, Fungal Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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