GM-CSF primes cardiac inflammation in a mouse model of Kawasaki disease

Kawasaki disease (KD) is the leading cause of pediatric heart disease in developed countries. KD patients develop cardiac inflammation, characterized by an early infiltrate of neutrophils and monocytes that precipitates coronary arteritis. Although the early inflammatory processes are linked to card...

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Bibliographic Details
Published in:The Journal of experimental medicine 2016-09, Vol.213 (10), p.1983-1998
Main Authors: Stock, Angus T, Hansen, Jacinta A, Sleeman, Matthew A, McKenzie, Brent S, Wicks, Ian P
Format: Article
Language:English
Subjects:
Animals
Candida albicans
Candida albicans - metabolism
Cell Compartmentation
Chemokines - metabolism
Disease Models, Animal
Fibroblasts - metabolism
Fibroblasts - pathology
Granulocyte-Macrophage Colony-Stimulating Factor - deficiency
Granulocyte-Macrophage Colony-Stimulating Factor - metabolism
Hematopoiesis
Inflammation - complications
Inflammation - genetics
Inflammation - pathology
Kinetics
Mice, Inbred C57BL
Monocytes - pathology
Mucocutaneous Lymph Node Syndrome - complications
Mucocutaneous Lymph Node Syndrome - pathology
Myocardium - metabolism
Myocardium - pathology
Neutrophils - pathology
Organ Specificity
Radiation Tolerance
Signal Transduction
Vasculitis - complications
Vasculitis - pathology
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Summary:Kawasaki disease (KD) is the leading cause of pediatric heart disease in developed countries. KD patients develop cardiac inflammation, characterized by an early infiltrate of neutrophils and monocytes that precipitates coronary arteritis. Although the early inflammatory processes are linked to cardiac pathology, the factors that regulate cardiac inflammation and immune cell recruitment to the heart remain obscure. In this study, using a mouse model of KD (induced by a cell wall Candida albicans water-soluble fraction [CAWS]), we identify an essential role for granulocyte/macrophage colony-stimulating factor (GM-CSF) in orchestrating these events. GM-CSF is rapidly produced by cardiac fibroblasts after CAWS challenge, precipitating cardiac inflammation. Mechanistically, GM-CSF acts upon the local macrophage compartment, driving the expression of inflammatory cytokines and chemokines, whereas therapeutically, GM-CSF blockade markedly reduces cardiac disease. Our findings describe a novel role for GM-CSF as an essential initiating cytokine in cardiac inflammation and implicate GM-CSF as a potential target for therapeutic intervention in KD.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20151853