Multiple sclerosis and anti-Plasmodium falciparum innate immune response

Stefano Sotgiu, Anna R. Sannella, Bruno Conti, Giannina Arru, Maria Laura Fois, Alessandra Sanna, Carlo Severini, Maria Concetta Morale, Bianca Marchetti, Giulio Rosati, Salvatore Musumeci

Research output: Contribution to journalArticlepeer-review

Abstract

Several epidemiological investigations conducted in Sardinia, insular Italy, indicate that the strong selective pressure of malaria along the centuries may have concurred to the elevated genetic MS-risk in this region. To test such hypothesis in an experimental setting, we have compared the immune response to P. falciparum (the causative agent of malaria) in Sardinian MS patients relative to their ethnic healthy controls and control MS patients of different ethnicity. To this purpose, the P. falciparum-driven peripheral mononuclear cell proliferation, the production of pro-inflammatory cytokines of the innate immunity such as TNF-α, IL-6 and IL-12 and the ability to inhibit the parasite growth have been tested in relation to HLA-DR alleles and TNF promoter polymorphisms known of being associated to MS. We found that P. falciparum-induced proliferation, cytokine production and parasite killing are significantly augmented in Sardinian MS patients as compared to controls (p <0.01). Additionally, a correlation is found with genes associated to Sardinian MS, namely the TNF- 376A promoter polymorphism and the class II HLA-DRB1*0405 allele. In conclusion, we have found evidences that some genetic traits formerly selected to confer a protective responses to P. falciparum now partially contribute to the elevated MS susceptibility amongst Sardinians.

Original languageEnglish
Pages (from-to)201-207
Number of pages7
JournalJournal of Neuroimmunology
Volume185
Issue number1-2
DOIs
Publication statusPublished - Apr 2007

Keywords

  • HLA
  • Malaria
  • Multiple sclerosis
  • Plasmodium falciparum
  • TNF

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Clinical Neurology
  • Neurology

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