Related Experiment Video
Updated: Apr 15, 2026
Isolation and Identification of Extravascular Immune Cells of the Heart
Published on: August 23, 2018
Identification of Pathogenic Cardiac CD11c+ Macrophages in Nod1-Mediated Acute Coronary Arteritis
Yoshitomo Motomura1, Shunsuke Kanno1, Kenichi Asano1
1From the Division of Molecular Immunology, Research Center for Infectious Diseases, Medical Institute of Bioregulation (Y.M., S.Y.), Department of Pediatrics, Graduate School of Medical Sciences (Y.M., S.K., H.N., T.H.), Kyushu University, Fukuoka, Japan; Laboratory of Immune Regulation, School of Life Science, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan (K.A.); Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan (Y.H., H.K.); Laboratory for Cell Signaling, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan (T.S.); Laboratory for Cell Signaling, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Osaka, Japan (T.S.); Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan (H.H.); and Division of Molecular Immunology, Project for Host Response, Medical Mycology Research Center, Chiba University, Chiba, Japan (S.Y.).
Objective:
Nod1 is an intracellular pattern recognition receptor for bacterial peptidoglycan fragments. We previously reported that a synthetic Nod1 ligand, FK565, induced acute coronary arteritis in mice similar to that of Kawasaki disease. However, the molecular mechanisms underlying this characteristic inflammation have remained elusive.
Approach And Results:
We found that CD11c(+)MHC class II(+) cells accumulated in the heart of FK565-treated mice before arteritis development. Morphological features and gene expression signatures of the cardiac CD11c(+)MHC class II(+) cells suggested that this population is closely related to macrophages, and thus, we designated them cardiac CD11c(+) macrophages. Nod1 in nonhematopoietic cells, rather than hematopoietic cells, was required for the increase of cardiac CD11c(+) macrophages and arteritis development. Among nonhematopoietic cells, cardiac endothelial cells produced a large amount of chemokines in response to FK565. Endothelial cell-specific blockade of Nod1 signaling suppressed FK565-induced expression of these chemokines, accumulation of cardiac CD11c(+) macrophages, and subsequent coronary arteritis development. We also found that CCR2(+)Ly6C(hi) inflammatory monocytes in peripheral blood supplied precursors of cardiac CD11c(+) macrophages. CCR2-deficient mice or pertussis toxin-treated mice exhibited decreased numbers of cardiac CD11c(+) macrophages and reduced arteritis.
Conclusions:
These results suggest that Ly6C(hi) monocytes are recruited to FK565-activated endothelial cells to generate cardiac CD11c(+) macrophages, which play a pivotal role in the pathogenesis of acute coronary arteritis.
Insights
FK565-induced acute coronary arteritis involves Nod1 in nonhematopoietic cells, leading to cardiac CD11c(+) macrophage accumulation. Ly6C(hi) monocytes are recruited to activated endothelial cells, driving arteritis pathogenesis.
Area of Science:
- Immunology
- Cardiovascular Biology
- Infectious Disease
Background:
- Nod1 (nucleotide-binding oligomerization domain-containing protein 1) is an intracellular pattern recognition receptor.
- FK565, a synthetic Nod1 ligand, previously induced acute coronary arteritis in mice, mimicking Kawasaki disease.
- The precise molecular mechanisms behind this FK565-induced inflammation were not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying FK565-induced acute coronary arteritis.
- To identify the cell types and signaling pathways involved in the development of arteritis.
Main Methods:
- Analysis of cardiac immune cell populations in FK565-treated mice using flow cytometry and gene expression profiling.
- Investigating the role of Nod1 signaling in hematopoietic and nonhematopoietic cells.
- Utilizing endothelial cell-specific Nod1 blockade and CCR2-deficient mouse models.
Main Results:
- FK565 treatment led to the accumulation of CD11c(+)MHC class II(+) cells, identified as cardiac CD11c(+) macrophages, preceding arteritis.
- Nod1 signaling in nonhematopoietic cells, particularly cardiac endothelial cells, was crucial for macrophage recruitment and arteritis development.
- Cardiac endothelial cells produced chemokines in response to FK565, attracting CCR2(+)Ly6C(hi) inflammatory monocytes that differentiated into cardiac macrophages.
Conclusions:
- FK565-activated endothelial cells recruit Ly6C(hi) monocytes, which differentiate into cardiac CD11c(+) macrophages.
- These cardiac CD11c(+) macrophages play a critical role in the pathogenesis of acute coronary arteritis.
- The study highlights a nonhematopoietic cell-intrinsic Nod1-driven pathway in the development of FK565-induced arteritis.
More Related Videos
06:38Simultaneous 3D Analysis of Cardiac Damage and Immune Response in Reperfused Acute Myocardial Infarction Using Light Sheet Fluorescence Microscopy
Published on: September 26, 2025
06:43Quantitative Analysis and Characterization of Atherosclerotic Lesions in the Murine Aortic Sinus
Published on: December 7, 2013
Related Concept Videos
01:21Myocarditis I: Introduction
01:19Acute Coronary Syndrome II: Pathophysiology and Clinical Manifestations
01:27Myocarditis II: Clinical Features and Diagnostic Tests
01:26Coronary Artery Disease II: Pathophysiology