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.

1. Introduction

Gliotoxin (GTX) is a mycotoxin that was originally isolated from Gliocladium culture. However, it has been lately described that it could also be produced by other fungal species, e.g., Aspergillus fumigatus, Eurotium chevalieri, Trichoderma virens, Neosartorya pseudofischeri, and some Penicillium and Acremonium species [1]. GTX is considered a virulence factor; it intensifies fungal invasiveness [2] and reduces the specific immunity against the fungus [3]. Even though the denomination “gliotoxin” is being 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. The primary routes of infection are respiratory or traumatic inoculation with subsequent hematogenous or contiguous spreading [7]. Certain fungal species that are secluded in non-neuronal tissues can release toxins which can then reach distant tissues, including the CNS, and, in this case, destroy astrocytes and oligodendrocytes [8], which possibly contributes to exacerbate CNS inflammation.

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About the Author

Emily Rachal is co-owner of Texas Mold Inspectors, (or TMI), along with her husband, in the Houston, TX area.  After her family’s devastating experience that not only injured her whole family, but also resulted in the loss of their youngest son Malachi, she and her husband have dedicated their lives to now educating and assisting families affected by toxic mold with their state-licensed mold inspection company.

Emily is the founder and owner of MAM. Additionally, she has recently started a non-profit organization in the name of her youngest son, called Malachi’s Message Foundation, to aid in financial support and offer hope to families who feel isolated and are unable to afford all the complex obstacles of overcoming a toxic mold exposure.

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