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. 2011 Jan;79(1):146-52.
doi: 10.1128/IAI.01004-10. Epub 2010 Nov 8.

Differential regulation of kidney and spleen cytokine responses in mice challenged with pathology-standardized doses of Candida albicans mannosylation mutants

Luis Castillo  1 , Donna M MacCallum, Alistair J P Brown, Neil A R Gow, Frank C Odds
Affiliations

Differential regulation of kidney and spleen cytokine responses in mice challenged with pathology-standardized doses of Candida albicans mannosylation mutants

Luis Castillo et al. Infect Immun. 2011 Jan.

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, pmr1Δ mutant and mnt1/2Δ 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 1α (MIP-1α), MIP-1β, and MIP-2 were higher in the kidneys of mice challenged with the pmr1Δ mutant than in animals challenged with the other strains and were lower by day 3, suggesting an earlier host response to the pmr1Δ mutant. The production of these chemokines also diminished earlier than controls in mice infected with the mnt1/2Δ 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.

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Figures

FIG. 1.
FIG. 1.
Day 3 outcome score versus challenge dose for 5 C. albicans strains injected i.v. in BALB/c mice. Data show means ± standard errors of the means (SEMs) (error bars) for groups of mice (3 mice in each group).
FIG. 2.
FIG. 2.
Periodic acid-Schiff stain (PAS)-hematoxylin-stained sections of mouse kidneys. Samples from animals infected with the indicated C. albicans strain at 24 and 48 h. Hyphal elements (indicated by black arrow and red color) are surrounded by a purple-colored infiltrate of polymorphonuclear leukocytes. Bars, 50 μm.
FIG. 3.
FIG. 3.
Concentrations of IL-21 and RANTES in homogenates of kidney and spleen over 72 h after i.v. infection of BALB/c mice with five strains of C. albicans. An asterisk indicates statistically significant interstrain variation in the data (Kruskal-Wallis test; P < 0.01). The concentrations are shown as means ± SEMs (error bars) (n = 9). A small amount of jitter has been applied to the x-axis data to facilitate visualization of the points. The symbol key is included in the bottom left panel.
FIG. 4.
FIG. 4.
Changes in the levels of the five chemokines or cytokines produced in highest concentration in response to C. albicans over time. The symbol key is included in the MIG (spleen) panel.
FIG. 5.
FIG. 5.
Changes in the levels of the final five chemokines or cytokines assayed over time. The symbol key is included in the bottom right panel.
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