Fungal Morphogenetic Pathways Are Required for the Hallmark Inflammatory Response during Candida albicans Vaginitis

• DOI: 10.1128/iai.01417-13
• Publication Date: 2013-11-12T05:09:02Z
• Authors: Brian M. Peters; Glen E. Palmer; Andrea K. Nash; Elizabeth A. Lilly; Paul L. Fidel; Mairi C. Noverr
• Keywords: Inflammatory response

ABSTRACT Vulvovaginal candidiasis, caused primarily by Candida albicans , presents significant health issues for women of childbearing age. As a polymorphic fungus, the ability C. to switch between yeast and hyphal morphologies is considered its central virulence attribute. Armed with new criteria defining vaginitis immunopathology, purpose this study was determine whether yeast-to-hypha transition required hallmark inflammatory responses previously characterized during murine vaginitis. Kinetic analyses vaginal infection in C57BL/6 mice demonstrated that fungal burdens remained constant throughout observation period, while polymorphonuclear leukocyte (PMN), S100A8, interleukin-1β levels obtained from lavage fluid increased day 3 onward. Lactate dehydrogenase activity also positively correlated effectors innate immunity. Additionally, immunodepletion neutrophils infected confirmed nonprotective role PMNs Determination importance morphogenesis addressed two-pronged approach. Intravaginal inoculation strains deleted key transcriptional regulators ( bcr1 Δ/Δ, efg1 cph1 Δ/Δ Δ/Δ) controlling revealed crucial morphogenetic signaling through Efg1 and, lesser extent, Bcr1 pathways contributing immunopathology. Furthermore, overexpression transcription factors NRG1 UME6 maintain morphologies, respectively, generating immune vivo . These results highlight associated response as important components immunopathogenesis vaginitis, implications benign colonization symptomatic infection.