PMID- 21059878 OWN - NLM STAT- MEDLINE DCOM- 20110125 LR - 20230526 IS - 1098-5522 (Electronic) IS - 0019-9567 (Print) IS - 0019-9567 (Linking) VI - 79 IP - 1 DP - 2011 Jan TI - Differential regulation of kidney and spleen cytokine responses in mice challenged with pathology-standardized doses of Candida albicans mannosylation mutants. PG - 146-52 LID - 10.1128/IAI.01004-10 [doi] AB - Cell surface polysaccharides are key determinants of host responses to fungal infection. We determined the effects of alterations in Candida albicans cell surface polysaccharide composition and gross changes in the host immune response in groups of mice challenged intravenously with five C. albicans strains at doses adjusted to give equal disease progression 3 days later. The five strains used were the parental strain NGY152, two mutants with defective cell wall mannosylation, pmr1Delta mutant and mnt1/2Delta mutant, and the same two strains with a copy of PMR1 and MNT1 reintegrated, respectively. Renal and spleen levels of chemokines and cytokines previously shown to be key components of early host response to C. albicans were determined at intervals up to 3 days after challenge. By 12 h after C. albicans challenge, the levels of granulocyte colony-stimulating factor (G-CSF), keratinocyte-derived chemokine (KC), interleukin 6 (IL-6), monocyte chemotactic peptide 1 (MCP-1), macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, and MIP-2 were higher in the kidneys of mice challenged with the pmr1Delta mutant than in animals challenged with the other strains and were lower by day 3, suggesting an earlier host response to the pmr1Delta mutant. The production of these chemokines also diminished earlier than controls in mice infected with the mnt1/2Delta strain. Although these differences were statistically significant, their magnitude was seldom great, and no unambiguous evidence was obtained for individual responses specific to any cell surface glycosylation change. We conclude that complex, multifactorial local responses offset and obscure any differences resulting from differences in surface mannosylation of C. albicans strains when infection results from pathology-standardized challenges. FAU - Castillo, Luis AU - Castillo L AD - Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom. FAU - MacCallum, Donna M AU - MacCallum DM FAU - Brown, Alistair J P AU - Brown AJ FAU - Gow, Neil A R AU - Gow NA FAU - Odds, Frank C AU - Odds FC LA - eng GR - WT_/Wellcome Trust/United Kingdom GR - 076954/Z/05/Z/WT_/Wellcome Trust/United Kingdom GR - 080088/Z/06/Z/WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101108 PL - United States TA - Infect Immun JT - Infection and immunity JID - 0246127 RN - 0 (Antigens, Surface) RN - 0 (Polysaccharides) SB - IM MH - Animals MH - Antigens, Surface/genetics/*metabolism MH - Candida albicans/classification/*genetics MH - Candidiasis/immunology/microbiology MH - Cell Wall/chemistry/*metabolism MH - Female MH - Gene Expression Regulation, Fungal/physiology MH - Kidney/immunology/metabolism/pathology MH - Mice MH - Mice, Inbred BALB C MH - Mutation MH - Polysaccharides/chemistry/*metabolism MH - Spleen/immunology/metabolism PMC - PMC3019922 EDAT- 2010/11/10 06:00 MHDA- 2011/01/28 06:00 PMCR- 2011/07/01 CRDT- 2010/11/10 06:00 PHST- 2010/11/10 06:00 [entrez] PHST- 2010/11/10 06:00 [pubmed] PHST- 2011/01/28 06:00 [medline] PHST- 2011/07/01 00:00 [pmc-release] AID - IAI.01004-10 [pii] AID - 1004-10 [pii] AID - 10.1128/IAI.01004-10 [doi] PST - ppublish SO - Infect Immun. 2011 Jan;79(1):146-52. doi: 10.1128/IAI.01004-10. Epub 2010 Nov 8.