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Close Encounters of the First Kind: Innate Sensors and Multiple Sclerosis

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Abstract

Although autoimmune diseases by definition imply adaptive immune system pathologies, growing evidence points to the relevance of innate receptors in modulating the initiation and progression of the autoreactive response. Multiple sclerosis (MS) is a chronic autoimmune disease characterised by central nervous system (CNS) demyelination, inflammation and axonal damage, in which the role of several pathogens such as herpes viruses have long been described as potential triggers. Encounters of these pathogens with altered innate receptors in susceptible individuals might drive pathological autoreactivity and inflammation, overcoming tolerance and causing subsequent CNS damage. In particular, functional and genetic studies reveal that Toll-like receptor (TLR) 2 and the Nod-like receptor (NLR) P3 could be involved in MS pathogenesis, whereas TLR3, the triggering receptor expressed on myeloid cells (TREM)-2 and the C-type lectin receptors (CLRs) MBL and MASP-3 would have a putative protective role. A better understanding of these interactions will provide important insights into the aetiopathogenesis of MS and could help design potential targets for novel therapies.

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Acknowledgments

This study was supported by the FEDER-FIS, Fondo de Investigación Sanitaria of the Spanish Health, Social Services and Equality Ministry (FIS project #PI12/02759), the Ramon Areces Foundation, grant XVII Concurso Nacional de Ayudas a la Investigación and FIS grant Ref. PI14/00616; R.P.D. is supported by the “Ramon y Cajal” program (MINECO, Spain). We are grateful to Marina Lorne for her assistance with figure design.

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The authors state no conflicts of interest.

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Authors and Affiliations

  1. Department of Clinical Immunology and IdISSC, Hospital Universitario Clínico San Carlos, Madrid, Spain

    Lidia Fernández-Paredes & Silvia Sánchez-Ramón

  2. Laboratory of Immunogenetics of Diseases, IdiPAZ Institute for Health Research, La Paz University Hospital, Madrid, Spain

    Rebeca Pérez de Diego

  3. Department of Neurology, University General Hospital Gregorio Marañón, Madrid, Spain

    Clara de Andrés

  4. Department of Microbiology I, Complutense University School of Medicine, Madrid, Spain

    Silvia Sánchez-Ramón

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  1. Lidia Fernández-Paredes
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  2. Rebeca Pérez de Diego
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  3. Clara de Andrés
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  4. Silvia Sánchez-Ramón
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Correspondence to Silvia Sánchez-Ramón.

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Fernández-Paredes, L., de Diego, R.P., de Andrés, C. et al. Close Encounters of the First Kind: Innate Sensors and Multiple Sclerosis. Mol Neurobiol 54, 101–114 (2017). https://doi.org/10.1007/s12035-015-9665-5

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  • DOI: https://doi.org/10.1007/s12035-015-9665-5

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