Molecular Neurobiology

, Volume 54, Issue 1, pp 101–114 | Cite as

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

  • Lidia Fernández-Paredes
  • Rebeca Pérez de Diego
  • Clara de Andrés
  • Silvia Sánchez-Ramón


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.


Multiple sclerosis Pattern recognition receptors (PRRs) Pathogen-associated molecular patterns (PAMPs) Innate immunity Infectious Dysregulation 



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.

Conflict of interest

The authors state no conflicts of interest.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Lidia Fernández-Paredes
    • 1
  • Rebeca Pérez de Diego
    • 2
  • Clara de Andrés
    • 3
  • Silvia Sánchez-Ramón
    • 1
    • 4
  1. 1.Department of Clinical Immunology and IdISSCHospital Universitario Clínico San CarlosMadridSpain
  2. 2.Laboratory of Immunogenetics of Diseases, IdiPAZ Institute for Health ResearchLa Paz University HospitalMadridSpain
  3. 3.Department of NeurologyUniversity General Hospital Gregorio MarañónMadridSpain
  4. 4.Department of Microbiology IComplutense University School of MedicineMadridSpain

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