title: Differential adaptation of Candida albicans in vivo modulates immune recognition by dectin-1.
abstract: The β-glucan receptor Dectin-1 is a member of the C-type lectin family and functions as an innate pattern recognition receptor in antifungal immunity. In both mouse and man, Dectin-1 has been found to play an essential role in controlling infections with Candida albicans, a normally commensal fungus in man which can cause superficial mucocutaneous infections as well as life-threatening invasive diseases. Here, using in vivo models of infection, we show that the requirement for Dectin-1 in the control of systemic Candida albicans infections is fungal strain-specific; a phenotype that only becomes apparent during infection and cannot be recapitulated in vitro. Transcript analysis revealed that this differential requirement for Dectin-1 is due to variable adaptation of C. albicans strains in vivo, and that this results in substantial differences in the composition and nature of their cell walls. In particular, we established that differences in the levels of cell-wall chitin influence the role of Dectin-1, and that these effects can be modulated by antifungal drug treatment. Our results therefore provide substantial new insights into the interaction between C. albicans and the immune system and have significant implications for our understanding of susceptibility and treatment of human infections with this pathogen.
authors: Division of Immunology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa.
authors: Mohlopheni J
authors: MJ
authors: Marakalala
authors: Simon
authors: S
authors: Vautier
authors: Joanna
authors: J
authors: Potrykus
authors: Louise A
authors: LA
authors: Walker
authors: Kelly M
authors: KM
authors: Shepardson
authors: Alex
authors: A
authors: Hopke
authors: Hector M
authors: HM
authors: Mora-Montes
authors: Ann
authors: A
authors: Kerrigan
authors: Mihai G
authors: MG
authors: Netea
authors: Graeme I
authors: GI
authors: Murray
authors: Donna M
authors: DM
authors: Maccallum
authors: Robert
authors: R
authors: Wheeler
authors: Carol A
authors: CA
authors: Munro
authors: Neil A R
authors: NA
authors: Gow
authors: Robert A
authors: RA
authors: Cramer
authors: Alistair J P
authors: AJ
authors: Brown
authors: Gordon D
authors: GD
authors: Brown
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000235:genetics / Q000276:immunology*; D000077336:Caspofungin; D002473:Cell Wall / Q000737:chemistry / Q000187:drug effects*; D002686:Chitin / Q000378:metabolism; D054714:Echinocandins / Q000494:pharmacology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D055666:Lipopeptides; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051192:Receptors, Pattern Recognition / Q000276:immunology; D047071:beta-Glucans / Q000378:metabolism; D000099181:Dectin-1
chemical_list: D000935:Antifungal Agents; D000077336:Caspofungin; D002686:Chitin; D054714:Echinocandins; D037181:Lectins, C-Type; D055666:Lipopeptides; D051192:Receptors, Pattern Recognition; D047071:beta-Glucans; D000099181:Dectin-1
references: J Immunol. 2004 Mar 1;172(5):3059-69
references: 14978111
references: Proc Natl Acad Sci U S A. 2000 May 23;97(11):6102-7
references: 10811913
references: Cell Mol Immunol. 2012 May;9(3):276-86
references: 22543832
references: Future Microbiol. 2010 Jan;5(1):67-79
references: 20020830
references: Nat Rev Microbiol. 2008 Jan;6(1):67-78
references: 18079743
references: J Biol Chem. 2006 Mar 3;281(9):5771-9
references: 16371356
references: Microbes Infect. 2013 Apr;15(4):259-69
references: 23220005
references: Fungal Genet Biol. 2009 Feb;46(2):210-9
references: 19032986
references: Eukaryot Cell. 2007 Jun;6(6):1041-52
references: 17416899
references: Med Mycol. 2011 Jul;49(5):467-74
references: 21108572
references: J Pharmacol Exp Ther. 2008 Apr;325(1):115-23
references: 18171906
references: Nat Immunol. 2007 Jan;8(1):39-46
references: 17159982
references: J Immunol. 2006 May 1;176(9):5513-8
references: 16622020
references: Cell Host Microbe. 2012 May 17;11(5):425-35
references: 22607796
references: Eukaryot Cell. 2004 Oct;3(5):1076-87
references: 15470236
references: Med Mycol. 2006 Mar;44(2):149-57
references: 16519018
references: Infect Immun. 1996 May;64(5):1866-9
references: 8613406
references: Sci Transl Med. 2012 Dec 19;4(165):165rv13
references: 23253612
references: EMBO J. 2005 Mar 23;24(6):1277-86
references: 15729357
references: Genes Immun. 2008 Jun;9(4):338-48
references: 18418396
references: PLoS Pathog. 2008 Apr 04;4(4):e1000040
references: 18389063
references: Science. 2012 Jun 8;336(6086):1314-7
references: 22674328
references: Cytokine. 2012 Jan;57(1):89-97
references: 22129624
references: Yeast. 2007 Apr;24(4):289-96
references: 17397107
references: J Biol Chem. 2004 Apr 9;279(15):15183-95
references: 14739279
references: J Infect Dis. 2005 Sep 1;192(5):893-900
references: 16088840
references: Antimicrob Agents Chemother. 2012 Jan;56(1):208-17
references: 21986821
references: Mol Microbiol. 2007 Mar;63(6):1606-28
references: 17367383
references: Nat Immunol. 2007 Jan;8(1):31-8
references: 17159984
references: Cell Host Microbe. 2009 May 8;5(5):487-97
references: 19454352
references: J Immunol Methods. 2006 Jul 31;314(1-2):164-9
references: 16844139
references: Microbiology (Reading). 2008 Feb;154(Pt 2):510-520
references: 18227255
references: Infect Immun. 2011 May;79(5):1961-70
references: 21357722
references: PLoS Pathog. 2008 Dec;4(12):e1000227
references: 19057660
references: Eukaryot Cell. 2012 May;11(5):560-70
references: 22447924
references: Med Mycol. 2010 Nov;48(7):897-903
references: 20166865
references: J Immunol. 2009 Apr 15;182(8):4938-46
references: 19342673
references: J Infect Dis. 2002 May 15;185(10):1483-9
references: 11992285
references: Antimicrob Agents Chemother. 2005 Jun;49(6):2226-36
references: 15917516
references: Mol Microbiol. 2007 Dec;66(5):1164-73
references: 17971081
references: Fungal Genet Biol. 2008 Oct;45(10):1404-14
references: 18765290
references: Eukaryot Cell. 2010 Nov;9(11):1734-46
references: 20870877
references: Eukaryot Cell. 2009 Mar;8(3):373-87
references: 19151328
references: Eukaryot Cell. 2007 Dec;6(12):2184-93
references: 17933909
references: Infect Immun. 1982 Dec;38(3):1020-8
references: 6759403
references: Nat Immunol. 2012 Sep;13(9):817-22
references: 22910394
references: N Engl J Med. 2009 Oct 29;361(18):1760-7
references: 19864674
references: PLoS Pathog. 2010 Jan;6(1):e1000714
references: 20062524