Dendritic cells treated with crude Plasmodium berghei extracts acquire immune-modulatory properties and suppress the development of autoimmune neuroinflammation

Author(s)

Thome, Rodolfo ; Issayama, Luidy K. ; da Costa, Thiago Alves ; Gangi, Rosaria D. ; Ferreira, Isadora T. ; Raposo, Catarina ; Lopes, Stefanie C. P. ; da Cruz Hoefling, Maria Alice ; Costa, Fabio T. M. ; Verinaud, Liana

• Document type: Journal article
• Source: IMMUNOLOGY; v. 143, n. 2, p. 10-pg., 2014-10-01.

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. (AU)

• FAPESP's process: 13/01401-9 - Changes in the thymic microenvironment during the acute phase of experimental infection with Paracoccidioides brasiliensis
• Grantee: Rosária Di Gangi
• Support Opportunities: Scholarships in Brazil - Doctorate
• 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
• FAPESP's process: 12/22131-7 - Inflammation and cell death in thymic demise induced by Paracoccidioides brasiliensis
• Grantee: Thiago Alves da Costa
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 11/17965-3 - Effect of thymic atrophy induced by Plasmodium berghei infection in the establishment and course of experimental autoimmune encephalomyelitis (EAE)
• Grantee: Liana Maria Cardoso Verinaud
• Support Opportunities: Regular Research Grants