Inflammatory reactions activated by
pattern recognition receptors (
PRRs) on the membrane of innate immune cells play an important role in
atherosclerosis. Whether the
PRRs of the
C-type lectin receptor (CLR) family including
Dectin-2 may be involved in the pathogenesis of
atherosclerosis remains largely unknown. Recently, the CLR-adaptor molecule caspase recruitment domain family member 9 (CARD9) has been suggested to play a role in cardiovascular pathologies as it provides the link between CLR activation and transcription of inflammatory
cytokines as well as immune cell recruitment. We therefore evaluated whether hematopoietic deletion of
Dectin-2 or CARD9 reduces
inflammation and
atherosclerosis development.
Low-density lipoprotein receptor (Ldlr)-knockout mice were transplanted with bone marrow from wild-type, Dectin-2- or Card9-knockout mice and fed a Western-type diet containing 0.1% (w/w)
cholesterol. After 10 weeks,
lipid and inflammatory parameters were measured and
atherosclerosis development was determined. Deletion of hematopoietic
Dectin-2 or CARD9 did not influence plasma
triglyceride and
cholesterol levels. Deletion of hematopoietic
Dectin-2 did not affect atherosclerotic lesion area, immune cell composition, ex vivo
cytokine secretion by peritoneal cells or bone marrow derived macrophages. Unexpectedly, deletion of hematopoietic CARD9 increased atherosclerotic lesion formation and lesion severity. Deletion of hematopoietic CARD9 did also not influence circulating immune cell composition and peripheral
cytokine secretion. Besides a tendency to a reduced macrophage content within these lesions, plasma MCP-1 levels decreased upon WTD feeding. Deletion of hematopoietic
Dectin-2 did not influence
atherosclerosis development in hyperlipidemic mice. The absence of CARD9 unexpectedly increased atherosclerotic lesion size and severity, suggesting that the presence of CARD9 may protect against initiation of
atherosclerosis development.