Protection against Paracoccidioides brasiliensis infection in mice treated with modulated dendritic cells relies on inhibition of interleukin-10 production by CD8(+) T cells

Author(s)

da Costa, Thiago Alves ; Di Gangi, Rosaria ; Martins, Paula ; Figueiredo Longhini, Ana Leda ; Zanucoli, Fabio ; Rodrigues de Oliveira, Alexandre Leite ; Stach-Machado, Dagmar Ruth ; Burger, Eva ; Verinaud, Liana ; Thome, Rodolfo

• Document type: Journal article
• Source: IMMUNOLOGY; v. 146, n. 3, p. 10-pg., 2015-11-01.

Abstract

Paracoccidioidomycosis is a systemic infection prevalent in Latin American countries. Disease develops after inhalation of Paracoccidioides brasiliensis conidia followed by an improper immune activation by the host leucocytes. Dendritic cells (DCs) are antigen-presenting cells with the unique ability to direct the adaptive immune response by the time of activation of naive T cells. This study was conducted to test whether extracts of P. brasiliensis would induce maturation of DCs. We found that DCs treated with extracts acquired an inflammatory phenotype and upon adoptive transfer conferred protection to infection. Interestingly, interleukin-10 production by CD8(+) T cells was ablated following DC transfer. Further analyses showed that lymphocytes from infected mice were high producers of interleukin-10, with CD8(+) T cells being the main source. Blockage of cross-presentation to CD8(+) T cells by modulated DCs abolished the protective effect of adoptive transfer. Collectively, our data show that adoptive transfer of P. brasiliensis-modulated DCs is an interesting approach for the control of infection in paracoccidioidomycosis. (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: 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: 13/08194-9 - Changes in the thymic microenvironment by experimental Paracoccidioides brasiliensis infection
• Grantee: Liana Maria Cardoso Verinaud
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/02631-0 - Role of nitric oxide (NO) in the modulation of experimental autoimmune encephalomyelitis (EAE) after the adoptive transfer of tolerogenic dendritic cells: influence of the MyD88-mTOR-iNOS and STAT1/3-iNOS axis
• Grantee: Rodolfo Thomé
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• 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