Differential Regulation of Kidney and Spleen Cytokine Responses in Mice Challenged with Pathology-Standardized Doses of Candida albicans Mannosylation Mutants

Luis Carlos Castillo, Donna M. MacCallum, Alistair J. P. Brown, Neil A. R. Gow, Frank C. Odds (Corresponding Author)

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Abstract

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, pmr1 Delta mutant and mnt1/2 Delta 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 1 alpha (MIP-1 alpha), MIP-1 beta, and MIP-2 were higher in the kidneys of mice challenged with the pmr1 Delta mutant than in animals challenged with the other strains and were lower by day 3, suggesting an earlier host response to the pmr1 Delta mutant. The production of these chemokines also diminished earlier than controls in mice infected with the mnt1/2 Delta 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.
Original languageEnglish
Pages (from-to)146-152
Number of pages7
JournalInfection and Immunity
Volume79
Issue number1
Early online date8 Nov 2010
DOIs
Publication statusPublished - Jan 2011

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Candida albicans
Spleen
Pathology
Cytokines
Kidney
Chemokines
Polysaccharides
Chemokine CCL3
Mycoses
Granulocyte Colony-Stimulating Factor
Glycosylation
Cell Wall
Disease Progression
Monocytes
Interleukin-6
Peptides
Infection

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title = "Differential Regulation of Kidney and Spleen Cytokine Responses in Mice Challenged with Pathology-Standardized Doses of Candida albicans Mannosylation Mutants",
abstract = "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, pmr1 Delta mutant and mnt1/2 Delta 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 1 alpha (MIP-1 alpha), MIP-1 beta, and MIP-2 were higher in the kidneys of mice challenged with the pmr1 Delta mutant than in animals challenged with the other strains and were lower by day 3, suggesting an earlier host response to the pmr1 Delta mutant. The production of these chemokines also diminished earlier than controls in mice infected with the mnt1/2 Delta 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.",
author = "Castillo, {Luis Carlos} and MacCallum, {Donna M.} and Brown, {Alistair J. P.} and Gow, {Neil A. R.} and Odds, {Frank C.}",
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T1 - Differential Regulation of Kidney and Spleen Cytokine Responses in Mice Challenged with Pathology-Standardized Doses of Candida albicans Mannosylation Mutants

AU - Castillo, Luis Carlos

AU - MacCallum, Donna M.

AU - Brown, Alistair J. P.

AU - Gow, Neil A. R.

AU - Odds, Frank C.

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N2 - 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, pmr1 Delta mutant and mnt1/2 Delta 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 1 alpha (MIP-1 alpha), MIP-1 beta, and MIP-2 were higher in the kidneys of mice challenged with the pmr1 Delta mutant than in animals challenged with the other strains and were lower by day 3, suggesting an earlier host response to the pmr1 Delta mutant. The production of these chemokines also diminished earlier than controls in mice infected with the mnt1/2 Delta 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.

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, pmr1 Delta mutant and mnt1/2 Delta 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 1 alpha (MIP-1 alpha), MIP-1 beta, and MIP-2 were higher in the kidneys of mice challenged with the pmr1 Delta mutant than in animals challenged with the other strains and were lower by day 3, suggesting an earlier host response to the pmr1 Delta mutant. The production of these chemokines also diminished earlier than controls in mice infected with the mnt1/2 Delta 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.

U2 - 10.1128/IAI.01004-10

DO - 10.1128/IAI.01004-10

M3 - Article

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