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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

Candida specific T cells contribute to elevated production of encephalitogenic cytokines in the CNS. CNS eluted cells were restimulated with MOG or heat-killed C. albicans and TNF-α (a), IL-6 (b), IL-17 (c), IFN-γ (d), IL-2 (e), and IL-10 (f) levels were measured by ELISA. The results are expressed as median, 25–75% (box), and minimum-maximum (error bars) of 6 to 7 mice/group. Mann-Whitney test, ∗P < 0.05 and ∗∗P < 0.01 indicate statistical difference between EAE and EAE+Ca groups under the same in vitro stimulation.
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fig6: Candida specific T cells contribute to elevated production of encephalitogenic cytokines in the CNS. CNS eluted cells were restimulated with MOG or heat-killed C. albicans and TNF-α (a), IL-6 (b), IL-17 (c), IFN-γ (d), IL-2 (e), and IL-10 (f) levels were measured by ELISA. The results are expressed as median, 25–75% (box), and minimum-maximum (error bars) of 6 to 7 mice/group. Mann-Whitney test, ∗P < 0.05 and ∗∗P < 0.01 indicate statistical difference between EAE and EAE+Ca groups under the same in vitro stimulation.

Mentions: H&E staining clearly indicated a strong and similar inflammatory process in the brain and spinal cord of both EAE and EAE+Ca animals, as shown in Figure 5. This analogous inflammatory process was confirmed by a semiquantitative analysis done in both brain and spinal cord samples (data not shown). As expected, no inflammatory infiltrates were present in normal mice (Figures 5(a) and 5(d)). The amount of total leukocytes eluted from the CNS from both experimental groups was also similar as depicted in Figure 5(g). The percentage of CD3+CD4+ T cells was always higher in the EAE+Ca group, independently of their previous stimulation with MOG or heat-killed C. albicans yeasts (Figure 5(h)). Cells eluted from the CNS of both groups respond in a similar way to in vitro stimulation with MOG, that is, they produced similar amounts of TNF-α, IL-17, IFN-γ, IL-2, and IL-10 (Figure 6). However, cells eluted from mice previously infected with C. albicans (EAE+Ca group) produced much more TNF-α, IL-6, IL-17, IFN-γ, and IL-10 in response to C. albicans in vitro restimulation (Figure 6).


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)

Candida specific T cells contribute to elevated production of encephalitogenic cytokines in the CNS. CNS eluted cells were restimulated with MOG or heat-killed C. albicans and TNF-α (a), IL-6 (b), IL-17 (c), IFN-γ (d), IL-2 (e), and IL-10 (f) levels were measured by ELISA. The results are expressed as median, 25–75% (box), and minimum-maximum (error bars) of 6 to 7 mice/group. Mann-Whitney test, ∗P < 0.05 and ∗∗P < 0.01 indicate statistical difference between EAE and EAE+Ca groups under the same in vitro stimulation.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4417602&req=5

fig6: Candida specific T cells contribute to elevated production of encephalitogenic cytokines in the CNS. CNS eluted cells were restimulated with MOG or heat-killed C. albicans and TNF-α (a), IL-6 (b), IL-17 (c), IFN-γ (d), IL-2 (e), and IL-10 (f) levels were measured by ELISA. The results are expressed as median, 25–75% (box), and minimum-maximum (error bars) of 6 to 7 mice/group. Mann-Whitney test, ∗P < 0.05 and ∗∗P < 0.01 indicate statistical difference between EAE and EAE+Ca groups under the same in vitro stimulation.
Mentions: H&E staining clearly indicated a strong and similar inflammatory process in the brain and spinal cord of both EAE and EAE+Ca animals, as shown in Figure 5. This analogous inflammatory process was confirmed by a semiquantitative analysis done in both brain and spinal cord samples (data not shown). As expected, no inflammatory infiltrates were present in normal mice (Figures 5(a) and 5(d)). The amount of total leukocytes eluted from the CNS from both experimental groups was also similar as depicted in Figure 5(g). The percentage of CD3+CD4+ T cells was always higher in the EAE+Ca group, independently of their previous stimulation with MOG or heat-killed C. albicans yeasts (Figure 5(h)). Cells eluted from the CNS of both groups respond in a similar way to in vitro stimulation with MOG, that is, they produced similar amounts of TNF-α, IL-17, IFN-γ, IL-2, and IL-10 (Figure 6). However, cells eluted from mice previously infected with C. albicans (EAE+Ca group) produced much more TNF-α, IL-6, IL-17, IFN-γ, and IL-10 in response to C. albicans in vitro restimulation (Figure 6).

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