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Application of dendritic cells stimulated with Trichinella spiralis excretory–secretory antigens alleviates experimental autoimmune encephalomyelitis

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Abstract

The parasitic nematode, Trichinella spiralis (T. spiralis), exerts an immunomodulatory effect on the host immune response through excretory–secretory products (ES L1) released from encysted muscle larvae. Our model of combined T. spiralis infection and experimental autoimmune encephalomyelitis (EAE) in Dark Agouti (DA) rats demonstrated a significant reduction in EAE severity in infected animals. Recently, we have created an immune status characteristic for the live infection by in vivo application of dendritic cells (DCs) stimulated with ES L1 products of T. spiralis muscle larvae. Moreover, these cells were able to ameliorate EAE when applied 7 days before EAE induction. ES L1-stimulated DCs increased production of IL-4, IL-10 and TGF-β, and decreased production of IFN-γ and IL-17, both at the systemic level and in target organs. A significant increase in the proportion of CD4+CD25+Foxp3+ T cells was found among spleen cells, and CNS infiltrates from DA rats treated with ES L1-stimulated DCs before EAE induction, compared to controls injected with unstimulated DCs. Regulatory T cells, together with elevated levels of IL-10 and TGF-β, are most likely involved in restraining the production of Th1 and Th17 cytokines responsible for autoimmunity and thus are responsible for the beneficial effect of ES L1-educated DCs on the course of EAE. Our results show that ES L1 antigen-stimulated DCs are able not only to provoke, but also to sustain anti-inflammatory and regulatory responses regardless of EAE induction, with subsequent amelioration of EAE, or even protection from the disease.

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Acknowledgments

We are grateful to Prof. Dr. Miodrag Colic and Dr. Sergej Tomic (Military Medical Academy School of Medicine, Belgrade) for valuable assistance and helpful discussions. We also wish to express sincere thanks to Dr. Marija Mostarica-Stojkovic (Institute of Microbiology and Immunology, School of Medicine, University of Belgrade) for critical reading of the paper and providing valuable advices. This work was supported by the Ministry of Education and Science, Republic of Serbia (Project 173047).

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Authors and Affiliations

  1. Institute for the Application of Nuclear Energy (INEP), University of Belgrade, Banatska 31b, 11080, Belgrade, Serbia

    Lj. Sofronic-Milosavljevic, I. Radovic, N. Ilic, J. Cvetkovic & A. Gruden-Movsesijan

  2. Institute for Medical Research, Military Academy, Crnotravska 17, 11000, Belgrade, Serbia

    I. Majstorovic

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  1. Lj. Sofronic-Milosavljevic
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  2. I. Radovic
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  6. A. Gruden-Movsesijan
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Correspondence to A. Gruden-Movsesijan.

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Sofronic-Milosavljevic, L., Radovic, I., Ilic, N. et al. Application of dendritic cells stimulated with Trichinella spiralis excretory–secretory antigens alleviates experimental autoimmune encephalomyelitis. Med Microbiol Immunol 202, 239–249 (2013). https://doi.org/10.1007/s00430-012-0286-6

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