Adjuvant and antigenic properties of Mycobacterium avium subsp. paratuberculosis on experimental autoimmune
Davide Cossu1, Kazumasa Yokoyama2, Tamami Sakanishi3
1Juntendo University, Department of Neurology, Tokyo, Japan; Juntendo University, Advanced Research Institute for Health Science, Tokyo, Japan.
Abstract:
Mycobacterium avium subsp. paratuberculosis (MAP), the causative agent of Johne's disease in ruminants, has been linked as a possible risk factor for human multiple sclerosis. In the current study we investigated the adjuvant effect of MAP on experimental autoimmune encephalomyelitis (EAE). Groups of C57BL/6 mice were actively immunized with myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide emulsified in incomplete Freund's adjuvant modified containing heat-killed MAP (MIFA). MOG-MIFA immunized mice showed an early disease onset and more severe clinical scores in comparison with MOG-CFA immunized mice, demonstrating for the first time the adjuvant effect of MAP on EAE development.
Insights
Mycobacterium avium subsp. paratuberculosis (MAP) acts as an adjuvant, worsening experimental autoimmune encephalomyelitis (EAE) in mice. This suggests MAP may exacerbate multiple sclerosis risk in humans.
Area of Science:
- Immunology
- Neuroscience
- Microbiology
Background:
- Mycobacterium avium subsp. paratuberculosis (MAP) is linked to Johne's disease in ruminants.
- MAP is a potential risk factor for human multiple sclerosis (MS).
- The adjuvant properties of MAP in the context of neuroinflammation are not well understood.
Purpose of the Study:
- To investigate the adjuvant effect of MAP on experimental autoimmune encephalomyelitis (EAE), an animal model for MS.
- To determine if MAP can enhance the autoimmune response in EAE.
Main Methods:
- C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein (MOG) peptide.
- Immunization was performed using incomplete Freund's adjuvant (CFA) or modified CFA containing heat-killed MAP (MIFA).
- Clinical scores and disease onset were monitored to assess EAE severity.
Main Results:
- Mice immunized with MOG-MIFA exhibited an earlier onset of EAE compared to MOG-CFA controls.
- MOG-MIFA immunized mice displayed more severe clinical scores throughout the disease course.
- These findings demonstrate a significant adjuvant effect of MAP in the EAE model.
Conclusions:
- Heat-killed Mycobacterium avium subsp. paratuberculosis acts as an adjuvant in EAE.
- MAP can exacerbate autoimmune neuroinflammation, supporting its potential role in MS pathogenesis.
- Further research is warranted to elucidate the mechanisms underlying MAP's adjuvant activity in EAE.
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