RNA-seq expression profiling of cardiac macrophages and splenic monocytes from naïve and CAWS challenged mice

The adult heart contains macrophages derived from both embryonic and adult bone-marrow derived precursors. Such population diversity raises the possibility that macrophages of distinct origins occupy differing biological roles or anatomical niches within the heart. Here, we provide evidence for the latter, showing that bone-marrow derived macrophages express the chemokine receptor Ccr2 and preferentially localise to the aortic root of the heart. This targeted migration occurs via a Ccr2-Ccl7 axis, whereby Ccl7-producing cardiac fibroblasts populating the aortic root, recruit Ccr2pos macrophages. Notably, the selective recruitment of Ccr2pos macrophages renders the aortic root sensitive to inflammatory disease. In a mouse model of Kawasaki Disease, acute inflammation drives a numerical increase in bone-marrow derived Ccr2pos macrophages, which accumulate at the aorta and trigger local inflammation at this site. We propose that cardiac fibroblasts recruit Ccr2pos macrophages to the aortic root, and that this process targets inflammatory disease to the heart's major vessels. Overall design: Mice were either naïve or challenged with a Candida albicans water-soluble complex (CAWS) to induce a mouse model of Kawasaki Disease. Cardiac macrophages were extracted from three independent pools of naive mice and three independent pools of CAWS challenged mice. Splenic monocytes were extracted from three independent pools of naive mice. In each case, cardiac macrophages were divided into three subpopulations (R1, R2 and R3) based on Ccr2 and MHC-II expression.

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Stock AT, Collins N, Smyth GK, Hu Y, Hansen JA, D'Silva DB, Jama HA, Lew AM, Gebhardt T, McLean CA, Wicks IP