Expression of Dectin-1 and Enhanced Activation of NALP3 Inflammasome Are Associated with Resistance to Paracoccidioidomycosis
Dectin-1 is a pattern recognition receptor (PRR) that recognizes β-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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-09-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.00913/full |
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| author | Vera Lucia Garcia Calich Claudia eFeriotti Silvia B. Bazan Flavio Vieira Loures Eliseu Frank Araujo Tania A. Costa |
| author_facet | Vera Lucia Garcia Calich Claudia eFeriotti Silvia B. Bazan Flavio Vieira Loures Eliseu Frank Araujo Tania A. Costa |
| author_sort | Vera Lucia Garcia Calich |
| collection | DOAJ |
| description | Dectin-1 is a pattern recognition receptor (PRR) that recognizes β-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 (A/J) 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 A/J macrophages. Curdlan up-regulated the expression of costimulatory molecules and PRRs in A/J 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 A/J macrophages but had not effect in B10.A cells. In contrast, laminarin reinforced the respective M2/M1 profiles of infected A/J and B10.A macrophages. Following curdlan treatment, A/J macrophages showed significantly higher Syk kinase phosphorylation and expression of intracellular pro-IL-1β . These findings led us to investigate if the NRLP3 inflammasome was differently activated in A/J and B10.A cells. Indeed, compared with B10.A cells A/J macrophages showed an increased expression of NALP3, ASC and IL-1β mRNA. They also showed elevated caspase-1 activity and secreted high levels of mature IL-β and IL-18 after curdlan treatment and P. brasiliensis infection. Our data demonstrate that soluble and particulate β-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. |
| first_indexed | 2024-04-12T11:50:59Z |
| format | Article |
| id | doaj.art-df217e2d80594dba9d674c0eb59a48df |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-12T11:50:59Z |
| publishDate | 2015-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-df217e2d80594dba9d674c0eb59a48df2022-12-22T03:34:10ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2015-09-01610.3389/fmicb.2015.00913147249Expression of Dectin-1 and Enhanced Activation of NALP3 Inflammasome Are Associated with Resistance to ParacoccidioidomycosisVera Lucia Garcia Calich0Claudia eFeriotti1Silvia B. Bazan2Flavio Vieira Loures3Eliseu Frank Araujo4Tania A. Costa5University of Sao PauloUniversity of Sao PauloUniversity of Sao PauloUniversity of Sao PauloUniversity of Sao PauloUniversity of Sao PauloDectin-1 is a pattern recognition receptor (PRR) that recognizes β-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 (A/J) 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 A/J macrophages. Curdlan up-regulated the expression of costimulatory molecules and PRRs in A/J 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 A/J macrophages but had not effect in B10.A cells. In contrast, laminarin reinforced the respective M2/M1 profiles of infected A/J and B10.A macrophages. Following curdlan treatment, A/J macrophages showed significantly higher Syk kinase phosphorylation and expression of intracellular pro-IL-1β . These findings led us to investigate if the NRLP3 inflammasome was differently activated in A/J and B10.A cells. Indeed, compared with B10.A cells A/J macrophages showed an increased expression of NALP3, ASC and IL-1β mRNA. They also showed elevated caspase-1 activity and secreted high levels of mature IL-β and IL-18 after curdlan treatment and P. brasiliensis infection. Our data demonstrate that soluble and particulate β-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.http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.00913/fullinnate immunityParacoccidioides brasiliensisNLRP3 inflammasomeM1/M2 macrophagesDectin-1 ReceptorResistance to Paracoccidioidomycosis |
| spellingShingle | Vera Lucia Garcia Calich Claudia eFeriotti Silvia B. Bazan Flavio Vieira Loures Eliseu Frank Araujo Tania A. Costa Expression of Dectin-1 and Enhanced Activation of NALP3 Inflammasome Are Associated with Resistance to Paracoccidioidomycosis Frontiers in Microbiology innate immunity Paracoccidioides brasiliensis NLRP3 inflammasome M1/M2 macrophages Dectin-1 Receptor Resistance to Paracoccidioidomycosis |
| title | Expression of Dectin-1 and Enhanced Activation of NALP3 Inflammasome Are Associated with Resistance to Paracoccidioidomycosis |
| title_full | Expression of Dectin-1 and Enhanced Activation of NALP3 Inflammasome Are Associated with Resistance to Paracoccidioidomycosis |
| title_fullStr | Expression of Dectin-1 and Enhanced Activation of NALP3 Inflammasome Are Associated with Resistance to Paracoccidioidomycosis |
| title_full_unstemmed | Expression of Dectin-1 and Enhanced Activation of NALP3 Inflammasome Are Associated with Resistance to Paracoccidioidomycosis |
| title_short | Expression of Dectin-1 and Enhanced Activation of NALP3 Inflammasome Are Associated with Resistance to Paracoccidioidomycosis |
| title_sort | expression of dectin 1 and enhanced activation of nalp3 inflammasome are associated with resistance to paracoccidioidomycosis |
| topic | innate immunity Paracoccidioides brasiliensis NLRP3 inflammasome M1/M2 macrophages Dectin-1 Receptor Resistance to Paracoccidioidomycosis |
| url | http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.00913/full |
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