title: Exacerbation of autoimmune neuro-inflammation in mice cured from blood-stage Plasmodium berghei infection.
abstract: The thymus plays an important role shaping the T cell repertoire in the periphery, partly, through the elimination of inflammatory auto-reactive cells. It has been shown that, during Plasmodium berghei infection, the thymus is rendered atrophic by the premature egress of CD4+CD8+ double-positive (DP) T cells to the periphery. To investigate whether autoimmune diseases are affected after Plasmodium berghei NK65 infection, we immunized C57BL/6 mice, which was previously infected with P. berghei NK65 and treated with chloroquine (CQ), with MOG35-55 peptide and the clinical course of Experimental Autoimmune Encephalomyelitis (EAE) was evaluated. Our results showed that NK65+CQ+EAE mice developed a more severe disease than control EAE mice. The same pattern of disease severity was observed in MOG35-55-immunized mice after adoptive transfer of P. berghei-elicited splenic DP-T cells. The higher frequency of IL-17+- and IFN-γ+-producing DP lymphocytes in the Central Nervous System of these mice suggests that immature lymphocytes contribute to disease worsening. To our knowledge, this is the first study to integrate the possible relationship between malaria and multiple sclerosis through the contribution of the thymus. Notwithstanding, further studies must be conducted to assert the relevance of malaria-induced thymic atrophy in the susceptibility and clinical course of other inflammatory autoimmune diseases.
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Thomé
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil.
authors.forename: André Luis
authors.initials: AL
authors.lastname: Bombeiro
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil.
authors.forename: Luidy Kazuo
authors.initials: LK
authors.lastname: Issayama
authors.affiliation: Department of Histology and Embryology, Institute of Biology, University of Campinas, Campinas, Brazil.
authors.forename: Catarina
authors.initials: C
authors.lastname: Rapôso
authors.affiliation: Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas, Campinas, Brazil.
authors.forename: Stefanie Costa Pinto
authors.initials: SC
authors.lastname: Lopes
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil.
authors.forename: Thiago Alves
authors.initials: TA
authors.lastname: da Costa
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil.
authors.forename: Rosária
authors.initials: R
authors.lastname: Di Gangi
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil.
authors.forename: Isadora Tassinari
authors.initials: IT
authors.lastname: Ferreira
authors.affiliation: Department of Hematology, Faculdade de Ciências Médicas, University of Campinas, Campinas, Brazil.
authors.forename: Ana Leda Figueiredo
authors.initials: AL
authors.lastname: Longhini
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil.
authors.forename: Alexandre Leite Rodrigues
authors.initials: AL
authors.lastname: Oliveira
authors.affiliation: Department of Histology and Embryology, Institute of Biology, University of Campinas, Campinas, Brazil.
authors.forename: Maria Alice
authors.initials: MA
authors.lastname: da Cruz Höfling
authors.affiliation: Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas, Campinas, Brazil.
authors.forename: Fábio Trindade Maranhão
authors.initials: FT
authors.lastname: Costa
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil.
authors.forename: Liana
authors.initials: L
authors.lastname: Verinaud
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002738:Chloroquine / Q000008:administration & dosage; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000382:microbiology; D007249:Inflammation / Q000276:immunology* / Q000382:microbiology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008288:Malaria / Q000150:complications / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D009103:Multiple Sclerosis / Q000150:complications / Q000276:immunology* / Q000382:microbiology; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000008:administration & dosage; D010446:Peptide Fragments / Q000008:administration & dosage; D010962:Plasmodium berghei / Q000276:immunology / Q000472:pathogenicity; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology*
chemical_list: D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C526792:myelin oligodendrocyte glycoprotein (35-50), Ala(37)-; D007371:Interferon-gamma; D002738:Chloroquine