Abstract
Gliotoxin (GTX) is the major and the most potent mycotoxin that is secreted by Aspergillus fumigatus, which is capable of injuring and killing microglial cells, astrocytes, and oligodendrocytes. During the last years, studies with patients and experimental models of multiple sclerosis (MS), which is an autoimmune disease of the central nervous system (CNS), suggested that fungal infections are among the possible initiators or aggravators of this pathology. The deleterious effect can occur through a direct interaction of the fungus with the CNS or by the toxin release from a non-neurological site. In the present work, we investigated the effect of GTX on experimental autoimmune encephalomyelitis (EAE) development. Female C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein and then intraperitoneally injected with three doses of GTX (1 mg/kg b.w., each) on days 4, 7, and 10. GTX aggravated clinical symptoms of the disease in a dose-dependent way and this outcome was concomitant with an increased neuroinflammation. CNS analyses revealed that GTX locally increased the relative expression of inflammatory genes and the cytokine production. Our results indicate that GTX administered in a non-neuronal site was able to increase neuroinflammation in EAE. Other mycotoxins could also be deleterious to many neurological diseases by similar mechanisms.
Highlights
Gliotoxin (GTX) is a mycotoxin that was originally isolated from Gliocladium culture
Induction, the EAE/GTX group presented a significantly higher maximum score, which corresponds to the mean of the highest degree of paralysis that was reached by all animals (Figure 1C), associated with a striking loss of body weight (Figure 1D)
We evaluated the effect of GTX in EAE, which is a murine model to study multiple sclerosis (MS)
Summary
Gliotoxin (GTX) is a mycotoxin that was originally isolated from Gliocladium culture. Toxins 2019, 11, 443 applied to both mycotoxins [4] and chemical compounds toxic for glial cells, as 3-chloropropanediol [5], the possible effects of fungi-derived GTX as triggers or aggravators of inflammatory central nervous system (CNS) disorders have not been comprehensively investigated so far. CNS fungal infections are associated with considerable morbidity and mortality and they comprise a wide spectrum of clinical syndromes, including abscesses, meningitis, meningoencephalitis, stroke, vasculitis, and spinal pathologies, such as arachnoiditis [6]. The main etiological agents of these infections are Aspergillus, Cryptococcus, Candida, Mucorales, dematiaceous molds, and dimorphic endemic fungi. Certain fungal species that are secluded in non-neuronal tissues can release toxins which can reach distant tissues, including the CNS, and, in this case, destroy astrocytes and oligodendrocytes [8], which possibly contributes to exacerbate
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