Role of innate and adaptive immune mechanisms in cardiac injury and repair

• Published in: Nature reviews. Immunology Vol. 15; no. 2; pp. 117 - 129
• Main Authors: Epelman, Slava, Liu, Peter P., Mann, Douglas L.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2015; Nature Publishing Group
• Subjects: 631/250/1619; 631/250/2504; 631/443/592/75/2/1674; 631/443/592/75/74; Adaptive Immunity; Animals; Biomedicine; Cardiovascular diseases; Care and treatment; Chemotaxis, Leukocyte - immunology; Fibrosis; Heart Diseases - immunology; Heart Diseases - metabolism; Heart Diseases - pathology; Humans; Immune System; Immunity, Innate; Immunology; Macrophages - immunology; Macrophages - metabolism; Myocarditis - immunology; Myocarditis - metabolism; Myocarditis - pathology; Neutrophil Infiltration - immunology; Neutrophils - immunology; Neutrophils - metabolism; Physiological aspects; review-article; Wound Healing - immunology; Wounds and injuries; Canada; United States
• ISSN: 1474-1733; 1474-1741; 1474-1741
• DOI: 10.1038/nri3800

Key Points Cardiac injury can lead to cardiomyocyte death, intense inflammation, scar formation and, over time, adverse cardiac remodelling. Following injury, cardiac inflammation is triggered by the release of conserved endogenous molecules and the production of pro-inflammatory cytokines and chemokines that lead to cellular infiltration. Early activation of mast cells leads to neutrophil recruitment, a robust inflammatory response and tissue damage. Recruited monocytes and resident macrophages modulate both tissue injury and tissue healing. Macrophage origin may dictate function in the heart. Primitive embryonically derived macrophages mediate cardiac tissue repair, whereas bone marrow-derived monocytes contribute to inflammation following cardiac injury. Lymphocytes and macrophages are involved in the complex transition from initial cardiac tissue inflammation to wound healing. This Review describes the immune responses that occur in the heart, explaining how different innate and adaptive immune cell populations can have beneficial or detrimental roles during cardiac tissue injury. In particular, the authors focus on the unique macrophage subsets that are found in the heart and their roles in regenerating damaged cardiac tissue. Despite the advances that have been made in developing new therapeutics, cardiovascular disease remains the leading cause of worldwide mortality. Therefore, understanding the mechanisms underlying cardiovascular tissue injury and repair is of prime importance. Following cardiac tissue injury, the immune system has an important and complex role in driving both the acute inflammatory response and the regenerative response. This Review summarizes the role of the immune system in cardiovascular disease — focusing on the idea that the immune system evolved to promote tissue homeostasis following injury and/or infection, and that the inherent cost of this evolutionary development is unwanted inflammatory damage.