Masking of β(1-3)-glucan in the cell wall of Candida albicans from detection by innate immune cells depends on phosphatidylserine.

Autor: Davis SE; Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA., Hopke A; Department of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, USA., Minkin SC Jr; Advanced Microscopy and Imaging Center, University of Tennessee, Knoxville, Tennessee, USA., Montedonico AE; Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA., Wheeler RT; Department of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, USA., Reynolds TB; Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA treynol6@utk.edu.
Jazyk: angličtina
Zdroj: Infection and immunity [Infect Immun] 2014 Oct; Vol. 82 (10), pp. 4405-13. Date of Electronic Publication: 2014 Aug 11.
DOI: 10.1128/IAI.01612-14
Abstrakt: The virulence of Candida albicans in a mouse model of invasive candidiasis is dependent on the phospholipids phosphatidylserine (PS) and phosphatidylethanolamine (PE). Disruption of the PS synthase gene CHO1 (i.e., cho1Δ/Δ) eliminates PS and blocks the de novo pathway for PE biosynthesis. In addition, the cho1Δ/Δ mutant's ability to cause invasive disease is severely compromised. The cho1Δ/Δ mutant also exhibits cell wall defects, and in this study, it was determined that loss of PS results in decreased masking of cell wall β(1-3)-glucan from the immune system. In wild-type C. albicans, the outer mannan layer of the wall masks the inner layer of β(1-3)-glucan from exposure and detection by innate immune effector molecules like the C-type signaling lectin Dectin-1, which is found on macrophages, neutrophils, and dendritic cells. The cho1Δ/Δ mutant exhibits increases in exposure of β(1-3)-glucan, which leads to greater binding by Dectin-1 in both yeast and hyphal forms. The unmasking of β(1-3)-glucan also results in increased elicitation of TNF-α from macrophages in a Dectin-1-dependent manner. The role of phospholipids in fungal pathogenesis is an emerging field, and this is the first study showing that loss of PS in C. albicans results in decreased masking of β(1-3)-glucan, which may contribute to our understanding of fungus-host interactions.
(Copyright © 2014, American Society for Microbiology. All Rights Reserved.)
Databáze: MEDLINE