Deletion of haematopoietic Dectin-2 or CARD9 does not protect from atherosclerosis development under hyperglycaemic conditions
2020
Thiem, Kathrin | Hoeke, Geerte | Zhou, Enchen | Hijmans, Anneke | Houben, Tom | Boels, Margien G. | Mol, Isabel M. | Lutgens, Esther | Shiri-Sverdlov, Ronit | Bussink, Johan | Kanneganti, Thirumala D. | Boon, Mariëtte R. | Stienstra, Rinke | Tack, Cees J. | Rensen, Patrick C.N. | Netea, Mihai G. | Berbée, Jimmy F.P. | Diepen, van, Janna A.
Background: C-type lectin receptors, including Dectin-2, are pattern recognition receptors on monocytes and macrophages that mainly recognize sugars and sugar-like structures present on fungi. Activation of C-type lectin receptors induces downstream CARD9 signalling, leading to the production of cytokines. We hypothesized that under hyperglycaemic conditions, as is the case in diabetes mellitus, glycosylated protein (sugar-like) structures activate C-type lectin receptors, leading to immune cell activation and increased atherosclerosis development. Methods: Low-density lipoprotein receptor-deficient mice were lethally irradiated and transplanted with bone marrow from control wild-type, Dectin-2<sup>−/−</sup> or Card9<sup>−/−</sup> mice. After 6 weeks of recovery, mice received streptozotocin injections (50 mg/g BW; 5 days) to induce hyperglycaemia. After an additional 2 weeks, mice were fed a Western-type diet (0.1% cholesterol) for 10 weeks. Results and Conclusion: Deletion of haematopoietic Dectin-2 reduced the number of circulating Ly6C<sup>hi</sup> monocytes, increased pro-inflammatory cytokine production, but did not affect atherosclerosis development. Deletion of haematopoietic CARD9 tended to reduce macrophage and collagen content in atherosclerotic lesions, again without influencing the lesion size. Deletion of haematopoietic Dectin-2 did not influence atherosclerosis development under hyperglycaemic conditions, despite some minor effects on inflammation. Deletion of haematopoietic CARD9 induced minor alterations in plaque composition under hyperglycaemic conditions, without affecting lesion size.
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