| Full text | |
| Author(s): |
Feriotti, Claudia
[1]
;
Bazan, Silvia B.
[1]
;
Loures, Flavio V.
[1]
;
Araujo, Eliseu F.
[1]
;
Costa, Tania A.
[1]
;
Calich, Vera L. G.
[1]
Total Authors: 6
|
| Affiliation: | [1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, Sao Paulo - Brazil
Total Affiliations: 1
|
| Document type: | Journal article |
| Source: | FRONTIERS IN MICROBIOLOGY; v. 6, SEP 3 2015. |
| Web of Science Citations: | 15 |
| Abstract | |
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) | |
| FAPESP's process: | 12/01765-8 - CHARACTERIZATION OF REGULATORY T CELLS IN LUNG PARACOCCIDIOIDOMYCOSIS (PCM) USING C57BL/6 MICE TRANSGENIC FOR FOXP3-GFP EXPRESSION |
| Grantee: | Silvia Boschi Bazan |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |