1. TLR3 essentially promotes protective class I-restricted memory CD8(+) T-cell responses to Aspergillus fumigatus in hematopoietic transplanted patients
- Author
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Rossana G. Iannitti, Francesca Fallarino, Antonio Pierini, Silvia Moretti, Jean-Paul Latgé, Carmen D'Angelo, Andrea Velardi, Katia Perruccio, Luigina Romani, Franco Aversa, Agostinho Carvalho, Silvia Bozza, Antonella De Luca, Cristina Cunha, and Universidade do Minho
- Subjects
Male ,Priming (immunology) ,CD8-Positive T-Lymphocytes ,Lymphocyte Activation ,Inbred C57BL ,Aspergillosis ,Biochemistry ,Aspergillus fumigatus ,Cohort Studies ,Mice ,0302 clinical medicine ,Cytotoxic T cell ,TLR3 ,Cells, Cultured ,Mice, Knockout ,Antigen Presentation ,0303 health sciences ,Cultured ,biology ,Effector ,Hematopoietic Stem Cell Transplantation ,Single Nucleotide ,Hematology ,Specific Pathogen-Free Organisms ,3. Good health ,Haematopoiesis ,Fungal ,Female ,Disease Susceptibility ,Antigens, Fungal ,Cells ,Knockout ,Immunology ,Antigen presentation ,Animals ,Dendritic Cells ,Fungal Vaccines ,Humans ,Mice, Inbred C57BL ,Polymorphism, Single Nucleotide ,Toll-Like Receptor 3 ,Immunocompromised Host ,Immunologic Memory ,CD8+ T cells ,03 medical and health sciences ,medicine ,Antigens ,Polymorphism ,030304 developmental biology ,Fungal vaccine ,Science & Technology ,Cell Biology ,biology.organism_classification ,medicine.disease ,Single nucleotide polymorphism ,030215 immunology - Abstract
Aspergillus fumigatus is a model fungal pathogen and a common cause of severe infections and diseases. CD8+ T cells are present in the human and murine T-cell repertoire to the fungus. However, CD8+ T-cell function in infection and the molecular mechanisms that control their priming and differentiation into effector and memory cells in vivo remain elusive. In the present study, we report that both CD4+ and CD8+ T cells mediate protective memory responses to the fungus contingent on the nature of the fungal vaccine. Mechanistically, class I MHC-restricted, CD8+ memory T cells were activated through TLR3 sensing of fungal RNA by cross-presenting dendritic cells. Genetic deficiency of TLR3 was associated with susceptibility to aspergillosis and concomitant failure to activate memory-protective CD8+ T cells both in mice and in patients receiving stem-cell transplantations. Therefore, TLR3 essentially promotes antifungal memory CD8+ T-cell responses and its deficiency is a novel susceptibility factor for aspergillosis in high-risk patients., These studies were supported by the Specific Targeted Research Project ALLFUN (FP7-HEALTH-2009 contract number 260338 to L.R.), by SYBARIS (FP7-HEALTH-2009 contract number 242220 to L.R.), and by the Italian Project AIDS 2010 by the Istituto Superiore di Sanita (contract number 40H40 to L.R.). A.C. and C.C. were supported by fellowships from Fundacao para a Ciencia e Tecnologia, Portugal (contracts SFRH/BPD/46292/2008 and SFRH/BD/65962/2009, respectively).
- Published
- 2012
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