Document Detail

Fungal morphogenetic pathways are required for the hallmark inflammatory response during Candida albicans vaginitis.
MedLine Citation:
PMID:  24478069     Owner:  NLM     Status:  MEDLINE    
Vulvovaginal candidiasis, caused primarily by Candida albicans, presents significant health issues for women of childbearing age. As a polymorphic fungus, the ability of C. albicans to switch between yeast and hyphal morphologies is considered its central virulence attribute. Armed with new criteria for defining vaginitis immunopathology, the purpose of this study was to determine whether the yeast-to-hypha transition is required for the hallmark inflammatory responses previously characterized during murine vaginitis. Kinetic analyses of vaginal infection with C. albicans in C57BL/6 mice demonstrated that fungal burdens remained constant throughout the observation period, while polymorphonuclear leukocyte (PMN), S100A8, and interleukin-1β levels obtained from vaginal lavage fluid increased by day 3 onward. Lactate dehydrogenase activity was also positively correlated with increased effectors of innate immunity. Additionally, immunodepletion of neutrophils in infected mice confirmed a nonprotective role for PMNs during vaginitis. Determination of the importance of fungal morphogenesis during vaginitis was addressed with a two-pronged approach. Intravaginal inoculation of mice with C. albicans strains deleted for key transcriptional regulators (bcr1Δ/Δ, efg1Δ/Δ, cph1Δ/Δ, and efg1Δ/Δ cph1Δ/Δ) controlling the yeast-to-hypha switch revealed a crucial role for morphogenetic signaling through the Efg1 and, to a lesser extent, the Bcr1 pathways in contributing to vaginitis immunopathology. Furthermore, overexpression of transcription factors NRG1 and UME6, to maintain yeast and hyphal morphologies, respectively, confirmed the importance of morphogenesis in generating innate immune responses in vivo. These results highlight the yeast-to-hypha switch and the associated morphogenetic response as important virulence components for the immunopathogenesis of Candida vaginitis, with implications for transition from benign colonization to symptomatic infection.
Brian M Peters; Glen E Palmer; Andrea K Nash; Elizabeth A Lilly; Paul L Fidel; Mairi C Noverr
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-11-11
Journal Detail:
Title:  Infection and immunity     Volume:  82     ISSN:  1098-5522     ISO Abbreviation:  Infect. Immun.     Publication Date:  2014 Feb 
Date Detail:
Created Date:  2014-01-30     Completed Date:  2014-04-08     Revised Date:  2014-08-03    
Medline Journal Info:
Nlm Unique ID:  0246127     Medline TA:  Infect Immun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  532-43     Citation Subset:  IM    
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MeSH Terms
Candida albicans / cytology*,  genetics*
Candidiasis, Vulvovaginal / microbiology*,  pathology*
Cytokines / immunology
Disease Models, Animal
Gene Deletion
L-Lactate Dehydrogenase / metabolism
Longitudinal Studies
Mice, Inbred C57BL
Neutrophils / immunology
Transcription Factors / genetics,  metabolism
Vaginal Douching
Virulence Factors / genetics*,  metabolism*
Grant Support
Reg. No./Substance:
0/Cytokines; 0/Transcription Factors; 0/Virulence Factors; EC Dehydrogenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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