Effect of Plasmodium berghei infection on experimental autoimmune encephalomyelitis

Author(s)

Rodolfo Thomé

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2014-06-30

Examining board members

Liana Maria Cardoso Verinaud; Dagmar Ruth Stach Machado; Wirla Maria da Silva Cunha Tamashiro; Alexandrina Sartori; Ramon Kaneno

• Advisor: Liana Maria Cardoso Verinaud

Abstract

Malaria remains as the most frequent infectious disease in the world, where half of the world population is at risk. Destruction of the causative agent, protozoan of the Plasmodium gender, is essential for the resolution of the disease and this is mediated by the coordinated action of both T and B lymphocytes. It has been demonstrated that malaria-bearing patients possess auto-antibodies, e in some cases, the worsening of autoimmune diseases such as lupus and multiple sclerosis. Studies, conducted by our group, have shown that P. berghei NK65 infection promoted thymic atrophy and the subsequent migration of CD4+CD8+ (DP) T cells towards the peripheral immune system. Since the thymus is the primary lymphoid organ responsible for the generation and maturation of T cells, playing a major role in the shaping of T cells repertoire, the present study aimed to investigate the influence of P. berghei infection in the clinical course of Experimental Autoimmune Encephalomyelitis (EAE), the mouse model for multiple sclerosis, and also over the maturation/activation status of dendritic cells. Results showed that malaria-cured mice developed a more severe EAE clinical course compared with control mice. The worsening in EAE score was related to the migration of DP-T cells towards the Central Nervous System (CNS), where these cells produced high amounts of inflammatory cytokines. Interestingly, EAE-resistant BALB/c mice developed the disease after plasmodia infection, indicating that the thymic atrophy induced by the infection is able to alter the susceptibility to autoimmune diseases. On the other hand, treatment of dendritic cells (DCs) with P.berghei extracts (PbX) modified their activation/maturation status towards a tolerogenic profile. The adoptive transfer of DC-PbX was able to suppress the development of EAE, as well as neuro-inflammation, through the reduction in cellular immune responses towards neuro-antigens. Taken together, the results collected in this study show that Plasmodium berghei NK65 infection promotes significant alterations in the immune system that aid the development of autoimmune neuro-inflammation. On the other hand, the use of plasmodia extracts may become an interesting approach to modulate inflammation through the adoptive transfer of tolerogenic dendritic cells (AU)

• FAPESP's process: 11/13191-3 - Effect of thymic atrophy induced by infection with Plasmodium berghei on the induction and development of EAE experimental
• Grantee: Rodolfo Thomé
• Support Opportunities: Scholarships in Brazil - Doctorate