Gliotoxin Aggravates Experimental Autoimmune Encephalomyelitis by Triggering Neuroinflammation
Gliotoxin (GTX) is the major and the most potent mycotoxin that is secreted by <i>Aspergillus fumigatus</i>, which is capable of injuring and killing microglial cells, astrocytes, and oligodendrocytes. During the last years, studies with patients and experimental models of multiple scler...
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MDPI AG
2019-07-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/11/8/443 |
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| author | Thais Fernanda de Campos Fraga-Silva Luiza Ayumi Nishiyama Mimura Laysla de Campos Toledo Leite Patrícia Aparecida Borim Larissa Lumi Watanabe Ishikawa James Venturini Maria Sueli Parreira de Arruda Alexandrina Sartori |
| author_facet | Thais Fernanda de Campos Fraga-Silva Luiza Ayumi Nishiyama Mimura Laysla de Campos Toledo Leite Patrícia Aparecida Borim Larissa Lumi Watanabe Ishikawa James Venturini Maria Sueli Parreira de Arruda Alexandrina Sartori |
| author_sort | Thais Fernanda de Campos Fraga-Silva |
| collection | DOAJ |
| description | Gliotoxin (GTX) is the major and the most potent mycotoxin that is secreted by <i>Aspergillus fumigatus</i>, 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. |
| first_indexed | 2024-04-11T20:56:42Z |
| format | Article |
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| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-11T20:56:42Z |
| publishDate | 2019-07-01 |
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| record_format | Article |
| series | Toxins |
| spelling | doaj.art-9798b740036c46fdaf08e4dbc439f7482022-12-22T04:03:39ZengMDPI AGToxins2072-66512019-07-0111844310.3390/toxins11080443toxins11080443Gliotoxin Aggravates Experimental Autoimmune Encephalomyelitis by Triggering NeuroinflammationThais Fernanda de Campos Fraga-Silva0Luiza Ayumi Nishiyama Mimura1Laysla de Campos Toledo Leite2Patrícia Aparecida Borim3Larissa Lumi Watanabe Ishikawa4James Venturini5Maria Sueli Parreira de Arruda6Alexandrina Sartori7Department of Microbiology and Immunology, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), Botucatu 18618-691, São Paulo, BrazilDepartment of Microbiology and Immunology, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), Botucatu 18618-691, São Paulo, BrazilDepartment of Biological Sciences, School of Sciences, São Paulo State University (UNESP), Bauru 17033-360, São Paulo, BrazilDepartment of Tropical Diseases and Image Diagnosis, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, São Paulo, BrazilDepartment of Microbiology and Immunology, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), Botucatu 18618-691, São Paulo, BrazilDepartment of Tropical Diseases and Image Diagnosis, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, São Paulo, BrazilDepartment of Biological Sciences, School of Sciences, São Paulo State University (UNESP), Bauru 17033-360, São Paulo, BrazilDepartment of Microbiology and Immunology, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), Botucatu 18618-691, São Paulo, BrazilGliotoxin (GTX) is the major and the most potent mycotoxin that is secreted by <i>Aspergillus fumigatus</i>, 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.https://www.mdpi.com/2072-6651/11/8/443multiple sclerosisexperimental autoimmune encephalomyelitismycotoxingliotoxinimmunomodulation |
| spellingShingle | Thais Fernanda de Campos Fraga-Silva Luiza Ayumi Nishiyama Mimura Laysla de Campos Toledo Leite Patrícia Aparecida Borim Larissa Lumi Watanabe Ishikawa James Venturini Maria Sueli Parreira de Arruda Alexandrina Sartori Gliotoxin Aggravates Experimental Autoimmune Encephalomyelitis by Triggering Neuroinflammation Toxins multiple sclerosis experimental autoimmune encephalomyelitis mycotoxin gliotoxin immunomodulation |
| title | Gliotoxin Aggravates Experimental Autoimmune Encephalomyelitis by Triggering Neuroinflammation |
| title_full | Gliotoxin Aggravates Experimental Autoimmune Encephalomyelitis by Triggering Neuroinflammation |
| title_fullStr | Gliotoxin Aggravates Experimental Autoimmune Encephalomyelitis by Triggering Neuroinflammation |
| title_full_unstemmed | Gliotoxin Aggravates Experimental Autoimmune Encephalomyelitis by Triggering Neuroinflammation |
| title_short | Gliotoxin Aggravates Experimental Autoimmune Encephalomyelitis by Triggering Neuroinflammation |
| title_sort | gliotoxin aggravates experimental autoimmune encephalomyelitis by triggering neuroinflammation |
| topic | multiple sclerosis experimental autoimmune encephalomyelitis mycotoxin gliotoxin immunomodulation |
| url | https://www.mdpi.com/2072-6651/11/8/443 |
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