Abstract
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(-/-) or Card9(-/-) 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(hi) 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.
Original language | English |
---|---|
Pages (from-to) | 1-12 |
Number of pages | 12 |
Journal | Diabetes & Vascular Disease Research |
Volume | 17 |
Issue number | 1 |
Early online date | 23 Dec 2019 |
DOIs | |
Publication status | Published - Jan 2020 |
Keywords
- Atherosclerosis
- CARD9
- C-type lectin receptors
- Dectin-2
- hyperglycaemia
- inflammation
- monocytes
- macrophages
- CARDIOVASCULAR-DISEASE
- LECTIN RECEPTORS
- EXPRESSION
- INFLAMMATION
- CHOLESTEROL
- LIGANDS
- RISK
- RAGE
- MICE
- TLR
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- 10.1177/1479164119892140Licence: CC BY-NC
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In: Diabetes & Vascular Disease Research, Vol. 17, No. 1, 01.2020, p. 1-12.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Deletion of haematopoietic Dectin-2 or CARD9 does not protect from atherosclerosis development under hyperglycaemic conditions
AU - Thiem, Kathrin
AU - Hoeke, Geerte
AU - Zhou, Enchen
AU - Hijmans, Anneke
AU - Houben, Tom
AU - Boels, Margien G.
AU - Mol, Isabel M.
AU - Lutgens, Esther
AU - Shiri-Sverdlov, Ronit
AU - Bussink, Johan
AU - Kanneganti, Thirumala D.
AU - Boon, Mariette R.
AU - Stienstra, Rinke
AU - Tack, Cees J.
AU - Rensen, Patrick C. N.
AU - Netea, Mihai G.
AU - Berbee, Jimmy F. P.
AU - van Diepen, Janna A.
N1 - Funding Information: Deletion of haematopoietic Dectin-2 reduced the number of circulating Ly6C hi 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. Atherosclerosis CARD9 C-type lectin receptors Dectin-2 hyperglycaemia inflammation monocytes/macrophages Nederlandse Organisatie voor Wetenschappelijk Onderzoek https://doi.org/10.13039/501100003246 #310372 Nederlandse Organisatie voor Wetenschappelijk Onderzoek https://doi.org/10.13039/501100003246 Spinoza Grant Nederlandse Organisatie voor Wetenschappelijk Onderzoek https://doi.org/10.13039/501100003246 Vedi Grant Nederlandse Organisatie voor Wetenschappelijk Onderzoek https://doi.org/10.13039/501100003246 Veni Grant Diabetes Fonds https://doi.org/10.13039/501100003092 #2013.81.1674 edited-state corrected-proof typesetter ts1 The authors thank Lianne van der Wee-Pals for her excellent technical assistance. Author contributions K.T., G.H., J.F.P.B. and J.A.v.D. conceived the study and designed experiments; K.T., G.H., A.H., T.H., M.G.B., I.M.M., M.R.B., J.B. and J.A.v.D. performed the experiments; K.T., G.H. and E.Z. analysed the data; K.T., G.H., E.L., R.S., C.J.T., M.G.N., P.C.N.R., J.F.P.B. and J.A.v.D. were involved in interpretation of the data; K.T., G.H., J.F.P.B. and J.A.v.D. drafted the article; all other authors revised the manuscript critically, and all authors approved the final version to be published. Availability of data and material All data generated or analysed during this study are included in this published article and its supplementary information files. Declaration of conflicting interests The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article. Ethical approval and consent to participate All experiments in this study were carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health, the Dutch Law on Animal Experiments and the FELASA regulations. The protocol was approved by the Ethics Committee on Animal Experiments of the Leiden University Medical Center. Funding The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This work was supported by the Dutch Diabetes Research Foundation (#2013.81.1674) and the Netherlands CardioVascular Research Initiative: The Dutch Heart Foundation, Dutch Federation of University Medical Centers, the Netherlands Organisation for Health Research and Development and the Royal Netherlands Academy of Sciences’ for the GENIUS project ‘Generating the best evidence-based pharmaceutical targets for atherosclerosis’ (CVON2011-9). R.S. is supported by a VIDI grant from the Netherlands Organisation for Scientific Research. M.G.N. is supported by an ERC Consolidator Grant (#310372) and a Spinoza Grant of the Netherlands Organisation for Scientific Research. J.A.v.D. is supported by a Veni Grant of the Netherlands Organisation for the Scientific Research (#91616083). ORCID iD Kathrin Thiem https://orcid.org/0000-0001-8144-1294 Supplemental material Supplemental material for this article is available online. Funding Information: The authors thank Lianne van der Wee-Pals for her excellent technical assistance. The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This work was supported by the Dutch Diabetes Research Foundation (#2013.81.1674) and the Netherlands CardioVascular Research Initiative: The Dutch Heart Foundation, Dutch Federation of University Medical Centers, the Netherlands Organisation for Health Research and Development and the Royal Netherlands Academy of Sciences? for the GENIUS project ?Generating the best evidence-based pharmaceutical targets for atherosclerosis? (CVON2011-9). R.S. is supported by a VIDI grant from the Netherlands Organisation for Scientific Research. M.G.N. is supported by an ERC Consolidator Grant (#310372) and a Spinoza Grant of the Netherlands Organisation for Scientific Research. J.A.v.D. is supported by a Veni Grant of the Netherlands Organisation for the Scientific Research (#91616083). Publisher Copyright: © The Author(s) 2020.
PY - 2020/1
Y1 - 2020/1
N2 - 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(-/-) or Card9(-/-) 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(hi) 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.
AB - 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(-/-) or Card9(-/-) 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(hi) 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.
KW - Atherosclerosis
KW - CARD9
KW - C-type lectin receptors
KW - Dectin-2
KW - hyperglycaemia
KW - inflammation
KW - monocytes
KW - macrophages
KW - CARDIOVASCULAR-DISEASE
KW - LECTIN RECEPTORS
KW - EXPRESSION
KW - INFLAMMATION
KW - CHOLESTEROL
KW - LIGANDS
KW - RISK
KW - RAGE
KW - MICE
KW - TLR
U2 - 10.1177/1479164119892140
DO - 10.1177/1479164119892140
M3 - Article
C2 - 31868000
SN - 1479-1641
VL - 17
SP - 1
EP - 12
JO - Diabetes & Vascular Disease Research
JF - Diabetes & Vascular Disease Research
IS - 1
ER -