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Experimental autoimmune encephalomyelitis development is aggravated by Candida albicans infection.

Fraga-Silva TF, Mimura LA, Marchetti CM, Chiuso-Minicucci F, França TG, Zorzella-Pezavento SF, Venturini J, Arruda MS, Sartori A - J Immunol Res (2015)

Bottom Line: EAE aggravation was associated with expansion of peripheral CD4(+) T cells and production of high levels of TNF-α, IFN-γ IL-6, and IL-17 by spleen and CNS cells.In addition to yeast and hyphae, fungus specific T cells were found in the CNS.Peripheral production of encephalitogenic cytokines could also contribute to disease aggravation.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Biosciences Institute, São Paulo State University (UNESP), 18618-000 Botucatu, SP, Brazil.

ABSTRACT
Multiple sclerosis (MS) is an inflammatory/autoimmune disease of the central nervous system (CNS) mainly mediated by myelin specific T cells. It is widely believed that environmental factors, including fungal infections, contribute to disease induction or evolution. Even though Candida infection among MS patients has been described, the participation of this fungus in this pathology is not clear. The purpose of this work was to evaluate the effect of a Candida albicans infection on experimental autoimmune encephalomyelitis (EAE) that is a widely accepted model to study MS. Female C57BL/6 mice were infected with C. albicans and 3 days later, animals were submitted to EAE induction by immunization with myelin oligodendrocyte glycoprotein. Previous infection increased the clinical score and also the body weight loss. EAE aggravation was associated with expansion of peripheral CD4(+) T cells and production of high levels of TNF-α, IFN-γ IL-6, and IL-17 by spleen and CNS cells. In addition to yeast and hyphae, fungus specific T cells were found in the CNS. These findings suggest that C. albicans infection before EAE induction aggravates EAE, and possibly MS, mainly by CNS dissemination and local induction of encephalitogenic cytokines. Peripheral production of encephalitogenic cytokines could also contribute to disease aggravation.

No MeSH data available.


Related in: MedlinePlus

Modulation of MOG-induced cytokine production by previous infection with C. albicans. C57BL/6 mice were infected with C. albicans and 3 days later they were submitted to EAE induction. Fourteen days after EAE induction, some immunological parameters were evaluated in the spleen. The percentage of CD3+CD4+ (a) and CD3+CD4+CD25+FoxP3+ (b) was performed by cytometric analysis in 100.000 acquired events. IL-10 (c), TNF-α (d), IL-6 (e), IL-17 (f), IFN-γ (g), IL-2 (h), and IL-4 (i) levels were measured in spleen cell cultures stimulated with MOG or heat-killed C. albicans. The results are expressed as mean ± SD (n = 6–8 mice/group). ANOVA, Tukey's test, and P < 0.05. Different letters indicate statistical difference among the groups (a and b) or among the groups under the same in vitro stimulation (c, d, e, f, g, h, and i).
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fig4: Modulation of MOG-induced cytokine production by previous infection with C. albicans. C57BL/6 mice were infected with C. albicans and 3 days later they were submitted to EAE induction. Fourteen days after EAE induction, some immunological parameters were evaluated in the spleen. The percentage of CD3+CD4+ (a) and CD3+CD4+CD25+FoxP3+ (b) was performed by cytometric analysis in 100.000 acquired events. IL-10 (c), TNF-α (d), IL-6 (e), IL-17 (f), IFN-γ (g), IL-2 (h), and IL-4 (i) levels were measured in spleen cell cultures stimulated with MOG or heat-killed C. albicans. The results are expressed as mean ± SD (n = 6–8 mice/group). ANOVA, Tukey's test, and P < 0.05. Different letters indicate statistical difference among the groups (a and b) or among the groups under the same in vitro stimulation (c, d, e, f, g, h, and i).

Mentions: To evaluate if peripheral immunological parameters could explain this detrimental fungal effect on EAE, we tested the % of CD3+CD4+ and CD3+CD4+CD25+ FoxP3+ T-cell subsets. The cytokine production by spleen cells restimulated with MOG or with heat-killed C. albicans yeasts was also determined. Normal mice and mice only infected were also analyzed. A higher percentage of CD3+CD4+ T cells were found in EAE+Ca and EAE groups in comparison to normal and infected groups. In addition, the % of this T-cell subset was significantly higher in the group that was previously infected with the fungus (EAE+Ca) in comparison to the EAE group (Figure 4(a)). The % of the FoxP3+ T cells was significantly higher in the EAE, but not in the Ca and EAE+Ca groups, in comparison to the control group, as illustrated in Figure 4(b). Concerning cytokines induced by MOG, the EAE+Ca group presented a significant production of TNF-α (Figure 4(d)), IL-6 (Figure 4(e)), and IL-17 (Figure 4(f)) in comparison to all other experimental groups. IL-2 (Figure 4(h)) and IL-4 (Figure 4(i)) were similarly elevated in EAE and EAE+Ca groups. These two groups also produced low and similar amounts of IL-10 (Figure 4(c)). Comparison of EAE+Ca and EAE cytokine production induced by heat-killed C. albicans clearly showed that IL-10, IL-6, IL-17, IFN-γ, IL-2, and IL-4 were significantly higher in the previously infected group.


Experimental autoimmune encephalomyelitis development is aggravated by Candida albicans infection.

Fraga-Silva TF, Mimura LA, Marchetti CM, Chiuso-Minicucci F, França TG, Zorzella-Pezavento SF, Venturini J, Arruda MS, Sartori A - J Immunol Res (2015)

Modulation of MOG-induced cytokine production by previous infection with C. albicans. C57BL/6 mice were infected with C. albicans and 3 days later they were submitted to EAE induction. Fourteen days after EAE induction, some immunological parameters were evaluated in the spleen. The percentage of CD3+CD4+ (a) and CD3+CD4+CD25+FoxP3+ (b) was performed by cytometric analysis in 100.000 acquired events. IL-10 (c), TNF-α (d), IL-6 (e), IL-17 (f), IFN-γ (g), IL-2 (h), and IL-4 (i) levels were measured in spleen cell cultures stimulated with MOG or heat-killed C. albicans. The results are expressed as mean ± SD (n = 6–8 mice/group). ANOVA, Tukey's test, and P < 0.05. Different letters indicate statistical difference among the groups (a and b) or among the groups under the same in vitro stimulation (c, d, e, f, g, h, and i).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4417602&req=5

fig4: Modulation of MOG-induced cytokine production by previous infection with C. albicans. C57BL/6 mice were infected with C. albicans and 3 days later they were submitted to EAE induction. Fourteen days after EAE induction, some immunological parameters were evaluated in the spleen. The percentage of CD3+CD4+ (a) and CD3+CD4+CD25+FoxP3+ (b) was performed by cytometric analysis in 100.000 acquired events. IL-10 (c), TNF-α (d), IL-6 (e), IL-17 (f), IFN-γ (g), IL-2 (h), and IL-4 (i) levels were measured in spleen cell cultures stimulated with MOG or heat-killed C. albicans. The results are expressed as mean ± SD (n = 6–8 mice/group). ANOVA, Tukey's test, and P < 0.05. Different letters indicate statistical difference among the groups (a and b) or among the groups under the same in vitro stimulation (c, d, e, f, g, h, and i).
Mentions: To evaluate if peripheral immunological parameters could explain this detrimental fungal effect on EAE, we tested the % of CD3+CD4+ and CD3+CD4+CD25+ FoxP3+ T-cell subsets. The cytokine production by spleen cells restimulated with MOG or with heat-killed C. albicans yeasts was also determined. Normal mice and mice only infected were also analyzed. A higher percentage of CD3+CD4+ T cells were found in EAE+Ca and EAE groups in comparison to normal and infected groups. In addition, the % of this T-cell subset was significantly higher in the group that was previously infected with the fungus (EAE+Ca) in comparison to the EAE group (Figure 4(a)). The % of the FoxP3+ T cells was significantly higher in the EAE, but not in the Ca and EAE+Ca groups, in comparison to the control group, as illustrated in Figure 4(b). Concerning cytokines induced by MOG, the EAE+Ca group presented a significant production of TNF-α (Figure 4(d)), IL-6 (Figure 4(e)), and IL-17 (Figure 4(f)) in comparison to all other experimental groups. IL-2 (Figure 4(h)) and IL-4 (Figure 4(i)) were similarly elevated in EAE and EAE+Ca groups. These two groups also produced low and similar amounts of IL-10 (Figure 4(c)). Comparison of EAE+Ca and EAE cytokine production induced by heat-killed C. albicans clearly showed that IL-10, IL-6, IL-17, IFN-γ, IL-2, and IL-4 were significantly higher in the previously infected group.

Bottom Line: EAE aggravation was associated with expansion of peripheral CD4(+) T cells and production of high levels of TNF-α, IFN-γ IL-6, and IL-17 by spleen and CNS cells.In addition to yeast and hyphae, fungus specific T cells were found in the CNS.Peripheral production of encephalitogenic cytokines could also contribute to disease aggravation.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Biosciences Institute, São Paulo State University (UNESP), 18618-000 Botucatu, SP, Brazil.

ABSTRACT
Multiple sclerosis (MS) is an inflammatory/autoimmune disease of the central nervous system (CNS) mainly mediated by myelin specific T cells. It is widely believed that environmental factors, including fungal infections, contribute to disease induction or evolution. Even though Candida infection among MS patients has been described, the participation of this fungus in this pathology is not clear. The purpose of this work was to evaluate the effect of a Candida albicans infection on experimental autoimmune encephalomyelitis (EAE) that is a widely accepted model to study MS. Female C57BL/6 mice were infected with C. albicans and 3 days later, animals were submitted to EAE induction by immunization with myelin oligodendrocyte glycoprotein. Previous infection increased the clinical score and also the body weight loss. EAE aggravation was associated with expansion of peripheral CD4(+) T cells and production of high levels of TNF-α, IFN-γ IL-6, and IL-17 by spleen and CNS cells. In addition to yeast and hyphae, fungus specific T cells were found in the CNS. These findings suggest that C. albicans infection before EAE induction aggravates EAE, and possibly MS, mainly by CNS dissemination and local induction of encephalitogenic cytokines. Peripheral production of encephalitogenic cytokines could also contribute to disease aggravation.

No MeSH data available.


Related in: MedlinePlus