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Article

Gliotoxin Aggravates Experimental Autoimmune Encephalomyelitis by Triggering Neuroinflammation

1
Department of Microbiology and Immunology, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), Botucatu 18618-691, São Paulo, Brazil
2
Department of Biological Sciences, School of Sciences, São Paulo State University (UNESP), Bauru 17033-360, São Paulo, Brazil
3
Department of Tropical Diseases and Image Diagnosis, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, São Paulo, Brazil
*
Author to whom correspondence should be addressed.
Toxins 2019, 11(8), 443; https://doi.org/10.3390/toxins11080443
Received: 24 June 2019 / Revised: 12 July 2019 / Accepted: 23 July 2019 / Published: 26 July 2019
(This article belongs to the Section Mycotoxins)
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. View Full-Text
Keywords: multiple sclerosis; experimental autoimmune encephalomyelitis; mycotoxin; gliotoxin; immunomodulation multiple sclerosis; experimental autoimmune encephalomyelitis; mycotoxin; gliotoxin; immunomodulation
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MDPI and ACS Style

Fraga-Silva, T.F.d.C.; Mimura, L.A.N.; Leite, L.d.C.T.; Borim, P.A.; Ishikawa, L.L.W.; Venturini, J.; Arruda, M.S.P.d.; Sartori, A. Gliotoxin Aggravates Experimental Autoimmune Encephalomyelitis by Triggering Neuroinflammation. Toxins 2019, 11, 443. https://doi.org/10.3390/toxins11080443

AMA Style

Fraga-Silva TFdC, Mimura LAN, Leite LdCT, Borim PA, Ishikawa LLW, Venturini J, Arruda MSPd, Sartori A. Gliotoxin Aggravates Experimental Autoimmune Encephalomyelitis by Triggering Neuroinflammation. Toxins. 2019; 11(8):443. https://doi.org/10.3390/toxins11080443

Chicago/Turabian Style

Fraga-Silva, Thais F.d.C.; Mimura, Luiza A.N.; Leite, Laysla d.C.T.; Borim, Patrícia A.; Ishikawa, Larissa L.W.; Venturini, James; Arruda, Maria S.P.d.; Sartori, Alexandrina. 2019. "Gliotoxin Aggravates Experimental Autoimmune Encephalomyelitis by Triggering Neuroinflammation" Toxins 11, no. 8: 443. https://doi.org/10.3390/toxins11080443

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