Exacerbation of autoimmune neuro-inflammation in mice cured from blood-stage Plasmodium berghei infection

• Published in: PloS one Vol. 9; no. 10; p. e110739
• Main Authors: Thomé, Rodolfo, Bombeiro, André Luis, Issayama, Luidy Kazuo, Rapôso, Catarina, Lopes, Stefanie Costa Pinto, da Costa, Thiago Alves, Di Gangi, Rosária, Ferreira, Isadora Tassinari, Longhini, Ana Leda Figueiredo, Oliveira, Alexandre Leite Rodrigues, da Cruz Höfling, Maria Alice, Costa, Fábio Trindade Maranhão, Verinaud, Liana
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17.10.2014; Public Library of Science (PLoS)
• Subjects: Adoptive transfer; Animals; Antigens; Atrophy; Autoimmune diseases; Bacterial infections; Biology; Biology and Life Sciences; CD4 antigen; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Central nervous system; Chemokines; Chloroquine; Chloroquine - administration & dosage; Cytokines; Dendritic cells; Disease; Disease control; Egress; Embryology; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - microbiology; Epidemiology; Experimental allergic encephalomyelitis; Health aspects; Histology; House mouse; Immunization; Infection; Infections; Inflammation; Inflammation - immunology; Inflammation - microbiology; Interferon-gamma - biosynthesis; Interferon-gamma - immunology; Interleukin 17; Laboratory animals; Lymphocytes; Lymphocytes T; Malaria; Malaria - complications; Malaria - immunology; Malaria - microbiology; Mice; Multiple sclerosis; Multiple Sclerosis - complications; Multiple Sclerosis - immunology; Multiple Sclerosis - microbiology; Myelin-Oligodendrocyte Glycoprotein - administration & dosage; Nervous system; Peptide Fragments - administration & dosage; Plasmodium; Plasmodium berghei; Plasmodium berghei - immunology; Plasmodium berghei - pathogenicity; Plasmodium falciparum; Spleen; T cells; T-Lymphocytes, Regulatory - immunology; Thymus; Thymus Gland - immunology; Vector-borne diseases; γ-Interferon; Brazil; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0110739

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.