title: Masking of β(1-3)-glucan in the cell wall of Candida albicans from detection by innate immune cells depends on phosphatidylserine.
abstract: 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.
authors.affiliation: Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Davis
authors.affiliation: Department of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Hopke
authors.affiliation: Advanced Microscopy and Imaging Center, University of Tennessee, Knoxville, Tennessee, USA.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Minkin
authors.affiliation: Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA.
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Montedonico
authors.affiliation: Department of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, USA.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Wheeler
authors.affiliation: Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA treynol6@utk.edu.
authors.forename: Todd B
authors.initials: TB
authors.lastname: Reynolds
mesh_terms: D002176:Candida albicans / Q000276:immunology*; D002473:Cell Wall / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D007113:Immunity, Innate; D037181:Lectins, C-Type / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D010718:Phosphatidylserines / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D047071:beta-Glucans / Q000276:immunology*; D000099181:Dectin-1
chemical_list: D037181:Lectins, C-Type; D010718:Phosphatidylserines; D014409:Tumor Necrosis Factor-alpha; D047071:beta-Glucans; D000099181:Dectin-1; C033363:beta-1,3-glucan
references.citation: Mol Microbiol. 2003 May;48(4):959-76
references.pmid: 12753189
references.citation: Lancet. 2002 Mar 30;359(9312):1135-44
references.pmid: 11943280
references.citation: J Exp Med. 2004 Jan 5;199(1):81-90
references.pmid: 14699082
references.citation: Curr Opin Struct Biol. 1995 Aug;5(4):521-7
references.pmid: 8528769
references.citation: Antimicrob Agents Chemother. 2000 Dec;44(12):3310-6
references.pmid: 11083633
references.citation: Eukaryot Cell. 2007 Nov;6(11):2092-101
references.pmid: 17905925
references.citation: Nat Immunol. 2007 Jan;8(1):31-8
references.pmid: 17159984
references.citation: J Biochem. 2001 May;129(5):843-9
references.pmid: 11328610
references.citation: Yeast. 1999 Nov;15(15):1609-18
references.pmid: 10572258
references.citation: Mol Gen Genet. 1984;198(2):179-82
references.pmid: 6394964
references.citation: Microbiology (Reading). 2010 Nov;156(Pt 11):3432-3444
references.pmid: 20688824
references.citation: Clin Infect Dis. 2001 Jan;32(1):50-62
references.pmid: 11118386
references.citation: Mol Microbiol. 2011 Feb;79(4):968-89
references.pmid: 21299651
references.citation: J Vis Exp. 2008 Jul 23;(17):
references.pmid: 19066523
references.citation: J Microbiol Methods. 2002 Mar;49(1):55-62
references.pmid: 11777582
references.citation: PLoS Genet. 2005 Jul;1(1):36-57
references.pmid: 16103911
references.citation: PLoS Pathog. 2006 Apr;2(4):e35
references.pmid: 16652171
references.citation: J Biol Chem. 1996 Apr 19;271(16):9193-6
references.pmid: 8621575
references.citation: Biochemistry. 1992 May 19;31(19):4667-73
references.pmid: 1581317
references.citation: Enferm Infecc Microbiol Clin. 2002 Nov;20(9):462-9; quiz 470, 479
references.pmid: 12425880
references.citation: Biochemistry. 1997 Nov 4;36(44):13579-85
references.pmid: 9354626
references.citation: Clin Infect Dis. 2001 Mar 1;32(5):686-93
references.pmid: 11229835
references.citation: J Immunol Methods. 2006 Jul 31;314(1-2):164-9
references.pmid: 16844139
references.citation: FEMS Yeast Res. 2006 Jan;6(1):14-29
references.pmid: 16423067
references.citation: PLoS Pathog. 2008 Dec;4(12):e1000227
references.pmid: 19057660
references.citation: Cell Microbiol. 2009 Jul;11(7):1007-15
references.pmid: 19388906
references.citation: Mol Microbiol. 2010 Mar;75(5):1112-32
references.pmid: 20132453
references.citation: Eukaryot Cell. 2012 Apr;11(4):532-44
references.pmid: 22286093
references.citation: Science. 2004 May 14;304(5673):1014-8
references.pmid: 15143282
references.citation: Cell. 1978 Sep;15(1):261-7
references.pmid: 212198
references.citation: Microbiology (Reading). 2006 Apr;152(Pt 4):905-912
references.pmid: 16549655
references.citation: Antimicrob Agents Chemother. 2005 Sep;49(9):3640-5
references.pmid: 16127033
references.citation: Front Biosci. 2008 May 01;13:3334-51
references.pmid: 18508436
references.citation: Methods Enzymol. 2002;350:42-71
references.pmid: 12073328
references.citation: Infect Immun. 1994 Jul;62(7):2761-72
references.pmid: 8005666
references.citation: Curr Opin Microbiol. 2011 Aug;14(4):392-9
references.pmid: 21803640
references.citation: Infect Immun. 2011 Nov;79(11):4472-9
references.pmid: 21875959
references.citation: Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8093-8
references.pmid: 9223320
references.citation: Nat Rev Microbiol. 2011 Dec 12;10(2):112-22
references.pmid: 22158429
references.citation: Nat Rev Immunol. 2004 Jan;4(1):1-23
references.pmid: 14661066
references.citation: Blood. 2004 Dec 15;104(13):4038-45
references.pmid: 15304394
references.citation: AIDS. 2012 Jul 31;26(12):1457-72
references.pmid: 22472853
references.citation: J Biol Chem. 1987 Jul 25;262(21):10109-13
references.pmid: 3611055