title: Dendritic cells treated with crude Plasmodium berghei extracts acquire immune-modulatory properties and suppress the development of autoimmune neuroinflammation.
abstract: Dendritic cells (DCs) are professional antigen-presenting cells specifically targeted during Plasmodium infection. Upon infection, DCs show impaired antigen presentation and T-cell activation abilities. In this study, we aimed to evaluate whether cellular extracts obtained from Plasmodium berghei-infected erythrocytes (PbX) modulate DCs phenotypically and functionally and the potential therapeutic usage of PbX-modulated DCs in the control of experimental autoimmune encephalomyelitis (EAE, the mouse model for human multiple sclerosis). We found that PbX-treated DCs have impaired maturation and stimulated the generation of regulatory T cells when cultured with naive T lymphocytes in vitro. When adoptively transferred to C57BL/6 mice the EAE severity was reduced. Disease amelioration correlated with a diminished infiltration of cytokine-producing T cells in the central nervous system as well as the suppression of encephalitogenic T cells. Our study shows that extracts obtained from P. berghei-infected erythrocytes modulate DCs towards an immunosuppressive phenotype. In addition, the adoptive transfer of PbX-modulated DCs was able to ameliorate EAE development through the suppression of specific cellular immune responses towards neuro-antigens. To our knowledge, this is the first study to present evidence that DCs treated with P. berghei extracts are able to control autoimmune neuroinflammation.
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Thomé
authors.forename: Luidy K
authors.initials: LK
authors.lastname: Issayama
authors.forename: Thiago
authors.initials: T
authors.lastname: Alves da Costa
authors.forename: Rosária D
authors.initials: RD
authors.lastname: Gangi
authors.forename: Isadora T
authors.initials: IT
authors.lastname: Ferreira
authors.forename: Catarina
authors.initials: C
authors.lastname: Rapôso
authors.forename: Stefanie C P
authors.initials: SC
authors.lastname: Lopes
authors.forename: Maria Alice
authors.initials: MA
authors.lastname: da Cruz Höfling
authors.forename: Fábio T M
authors.initials: FT
authors.lastname: Costa
authors.forename: Liana
authors.initials: L
authors.lastname: Verinaud
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000637:transplantation*; D005260:Female; D007111:Immunity, Cellular; D007165:Immunosuppression Therapy / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000517:prevention & control*; D010641:Phenotype; D010962:Plasmodium berghei / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D013997:Time Factors
chemical_list: D016207:Cytokines
keywords: Plasmodium extracts; dendritic cells; experimental autoimmune encephalomyelitis; neuroinflammation