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Dectin-1 and NOD2 mediate cathepsin activation in zymosan-induced arthritis in mice
Holly L Rosenzweig1, Jenna S Clowers, Gabriel Nunez
1Oregon Health and Science University, Mail stop: L467 AD, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA. rosenzwh@ohsu.edu
Objective:
Activation of pattern recognition receptors (PRR) may contribute to arthritis. Here, we elucidated the role of NOD2, a genetic cause of inflammatory arthritis, and several other PRR in a murine model of inflammatory arthritis.
Methods:
The roles of CR3, TLR2, MyD88, NOD1, NOD2, Dectin-1 and Dectin-2 were tested in vivo in arthritis elicited by intra-articular injections of zymosan, the fungal cell wall components curdlan, laminarin and mannan, and the bacterial cell wall peptidoglycan.
Results:
Dectin-1, and to a lesser extent Dectin-2, contributed to arthritis. TLR2, MyD88 and CR3 played non-essential roles. Observations based on injection of curdlan, laminarin or mannan supported the dominant role of the Dectin-1 pathway in the joint. We demonstrated differential roles for NOD1 and NOD2 and identified NOD2 as a novel and essential mediator of zymosan-induced arthritis.
Conclusions:
Together, Dectin-1 and NOD2 are critical, sentinel receptors in the arthritogenic effects of zymosan. Our data identify a novel role for NOD2 during inflammatory responses within joints.
Insights
Pattern recognition receptors (PRR) like Dectin-1 and NOD2 are crucial in causing arthritis. NOD2 is identified as a novel mediator in zymosan-induced inflammatory arthritis.
Area of Science:
- Immunology
- Rheumatology
Background:
- Pattern recognition receptors (PRR) are implicated in arthritis pathogenesis.
- NOD2 is a known genetic cause of inflammatory arthritis.
Purpose of the Study:
- To investigate the roles of various PRRs, including NOD2, in a murine model of inflammatory arthritis.
- To elucidate the specific contribution of NOD2 and other PRRs to arthritis induced by fungal and bacterial components.
Main Methods:
- In vivo testing of CR3, TLR2, MyD88, NOD1, NOD2, Dectin-1, and Dectin-2.
- Arthritis induction via intra-articular injections of zymosan, curdlan, laminarin, mannan, and peptidoglycan.
Main Results:
- Dectin-1 and Dectin-2 significantly contributed to arthritis.
- NOD2 was identified as a novel and essential mediator of zymosan-induced arthritis.
- TLR2, MyD88, and CR3 played non-essential roles.
Conclusions:
- Dectin-1 and NOD2 act as critical sentinel receptors in zymosan-induced arthritogenic effects.
- A novel role for NOD2 in mediating inflammatory responses within joints is identified.
