Recognition of alpha-mannan by dectin 2 is essential for onset of Kawasaki disease-like murine vasculitis induced by Candida albicans cell-wall polysaccharide

Abstract

Objectives: Using a murine model of systemic Kawasaki disease (KD)–like vasculitis induced by Candida albicans cell–wall–derived mannan · β–glucan · protein complexes, the objective was to elucidate the relationships of β–glucan receptor dectin–1 (D1) and α–mannan receptor dectin–2 (D2) to the onset of that vasculitis.

Methods: The incidence and histological severity of vasculitis were compared among mice lacking the genes for D1 or D2 (i.e. D1^−/− and D2^−/−) and wild–type (WT) mice.

Results: The incidences of vasculitis in the three animal groups were 100% (18/18) in the WT group, 100% (18/18) in the D1^−/− group, and 0% (0/18) in the D2^−/− group. In the WT and D1^−/− mice, severe inflammatory cell infiltration, consisting mainly of neutrophils and macrophages, was seen in the aortic root and the coronary arteries. On the other hand, in the D2^−/− mice, not even mild vascular lesions such as endoarteritis were seen.

Conclusion: Recognition of α–mannan by D2 played an important role in the onset of vasculitis in the studied murine model.

Keywords:

• Animal model
• Candida albicans
• dectin
• Kawasaki disease
• vasculitis

Acknowledgments

The authors are deeply indebted to Dr. Yoichiro Iwakura (Tokyo University of Science) for his helpful scientific advice. We sincerely thank Yuta Fujita and Mai Okabayashi for their skilled technical assistance in tissue specimen preparation and cytokine assays. Dr. Takashi Kajitani (Research Administrator of Toho University) kindly advised us regarding the statistical analyses. We also thank Lawrence W. Stiver for editing our manuscript.

Conflict of interest

None.

Additional information

Funding

This study was supported by a Toho University School of Medicine. Research Project Grant (28-38), the MEXT-Supported Program for the Strategic Research Foundation at Private Universities and a grant from Japan Kawasaki Disease Research Center.