title: Protection against Paracoccidioides brasiliensis infection in mice treated with modulated dendritic cells relies on inhibition of interleukin-10 production by CD8+ T cells.
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.
authors: Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
authors: Thiago Alves
authors: TA
authors: da Costa
authors: Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
authors: Rosária
authors: R
authors: Di Gangi
authors: Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
authors: Paula
authors: P
authors: Martins
authors: Department of Haematology, Faculdade de Ciências Médicas, University of Campinas, Campinas, SP, Brazil.
authors: Ana Leda Figueiredo
authors: AL
authors: Longhini
authors: Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
authors: Fábio
authors: F
authors: Zanucoli
authors: Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
authors: Alexandre Leite Rodrigues
authors: AL
authors: de Oliveira
authors: Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
authors: Dagmar Ruth
authors: DR
authors: Stach-Machado
authors: Instituto de Biociências, Universidade Federal de Alfenas, Alfenas, MG, Brazil.
authors: Eva
authors: E
authors: Burger
authors: Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
authors: Liana
authors: L
authors: Verinaud
authors: Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
authors: Rodolfo
authors: R
authors: Thomé
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000946:Antigens, Fungal / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D045142:Cross-Priming; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D005260:Female; D005657:Fungal Vaccines / Q000276:immunology / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010228:Paracoccidioides / Q000276:immunology*; D010229:Paracoccidioidomycosis / Q000276:immunology* / Q000517:prevention & control*
chemical_list: D000946:Antigens, Fungal; D016207:Cytokines; D005657:Fungal Vaccines; C556062:IL10 protein, mouse; D018836:Inflammation Mediators; D016753:Interleukin-10
keywords: Paracoccidioides brasiliensis; cell-based vaccine; dendritic cells; fungal infection; immunoregulation; paracoccidioidomycosis