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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Expression of dectin-1 and enhanced activation of NALP3 inflammasome are associated with resistance to paracoccidioidomycosis

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Feriotti, Claudia [1] ; Bazan, Silvia B. [1] ; Loures, Flavio V. [1] ; Araujo, Eliseu F. [1] ; Costa, Tania A. [1] ; Calich, Vera L. G. [1]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, Sao Paulo - Brazil
Número total de Afiliações: 1
Tipo de documento: Artigo Científico
Citações Web of Science: 15
Assunto(s):Paracoccidioides brasiliensis   Paracoccidioidomicose   beta-Glucanas

Dectin-1 is a pattern recognition receptor (PRR) that recognizes beta-glucans and plays a major role in the immunity against fungal pathogens. Paracoccidioides brasiliensis, the causative agent of paracoccidioidomycosis, has a sugar-rich cell wall mainly composed of mannans and glucans. To investigate the role of dectin-1 in the innate immunity of resistant (NJ) and susceptible (B10.A) mice to P brasiliensis infection, we evaluated the role of curdlan (a dectin-1 agonist) and laminarin (a dectin-1 antagonist) in the activation of macrophages from both mouse strains. We verified that curdlan has a negligible role in the activation of B10.A macrophages but enhances the phagocytic and fungicidal abilities of NJ macrophages. Curdlan up-regulated the expression of costimulatory molecules and PRRs in NJ macrophages that express elevated levels of dectin-1, but not in B10.A cells. In addition, curdlan treatment inhibited arginase-1 and enhanced NO-synthase mRNA expression in infected NJ macrophages but had not effect in B10.A cells. In contrast, laminarin reinforced the respective M2/M1 profiles of infected NJ and B1 0.A macrophages. Following curdlan treatment, NJ macrophages showed significantly higher Syk kinase phosphorylation and expression of intracellular pro-IL-1 beta than B10.A cells. These findings led us to investigate if the NRLP3 inflammasome was differently activated in NJ and B1 0.A cells. Indeed, compared with B1 0.A cells NJ macrophages showed an increased expression of NALP3, ASC, and IL-1 beta mRNA. They also showed elevated caspase-1 activity and secreted high levels of mature and IL-18 after curdlan treatment and P brasiliensis infection. Our data demonstrate that soluble and particulate -glucans exert opposed modulatory activities on macrophages of diverse genetic patterns. Moreover, the synergistic action of dectin-1 and NALP3 inflammasome were for the first time associated with the innate response of resistant hosts to P brasiliensis infection. (AU)

Processo FAPESP: 12/01765-8 - Caracterização das células t reguladoras na paracoccidioidomicose (pcm) pulmonar utilizando camundongos c57bl/6 transgênicos para a expressão de foxp3-gfp
Beneficiário:Silvia Boschi Bazan
Linha de fomento: Bolsas no Brasil - Pós-Doutorado