Involvement of innate and adaptive immunity in a murine model of coronary arteritis mimicking Kawasaki disease.
Kawasaki disease (KD) is the most common cause of acquired cardiac disease and acute vasculitis in children in the developed world. Injection of a cell wall extract isolated from Lactobacillus casei (LCCWE) into mice causes a focal coronary arteritis that histopathologically mimics the coronary lesions observed in KD patients. In this study we used this model to investigate the participation of T cells, B cells, and dendritic cells (DC) in the development of coronary arteritis. RAG1(-/-), B cell(null), and wild-type (WT) mice were injected with a single dose of LCCWE (500 microg/mouse i.p.). None of the RAG1(-/-) mice developed coronary arteritis, whereas 70% of WT and 100% of B cell(null) mice developed coronary lesions, indicating that T cells were required for lesion formation. When splenocytes isolated from LCCWE-treated mice were restimulated with LCCWE, we observed significant IFN-gamma secretion in WT but not in RAG1(-/-) mice. Immunohistochemical staining showed F4/80(+) macrophages, activated MIDC-8(+) myeloid DCs (mDC), plasmacytoid DCs, and colocalization of CD3(+) T cells with mDCs in coronary artery lesions, suggesting an Ag-driven process. T cells but not B cells are required for LCCWE-induced coronary arteritis. Similar to human lesions, the coronary lesions contain macrophages, activated mDCs, and plaslmacytoid DCs all in close proximity to T cells, further strengthening the relevance of this mouse model to the immunopathology of coronary disease in KD. These studies are consistent with the interpretation that macrophages and DCs may collaborate with T cells in the pathological mechanisms of coronary arteritis.
Pediatric Infectious Diseases, Cedars-Sinai Medical Center, University of California, Los Angeles, CA 90048, USA.
Danica J
DJ
Schulte
Atilla
A
Yilmaz
Kenichi
K
Shimada
Michael C
MC
Fishbein
Emily L
EL
Lowe
Shuang
S
Chen
Michelle
M
Wong
Terence M
TM
Doherty
Thomas
T
Lehman
Timothy R
TR
Crother
Rosalinda
R
Sorrentino
Moshe
M
Arditi
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D003324:Coronary Artery Disease / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007110:Immunity, Active; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007780:Lacticaseibacillus casei / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009080:Mucocutaneous Lymph Node Syndrome / Q000276:immunology* / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D018398:Homeodomain Proteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C064658:RAG-1 protein; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor