There are 12 times as many immune cells in the heart compared to skeletal muscle [1]. The immune response is divided into (1) the innate and (2) the humoral/adaptive responses. The innate immune system responds to molecular patterns found in pathogens (pathogen-associated molecular patterns, PAMPs) and to host proteins released following tissue injury (danger-associated molecular patterns, DAMPs). Following activation, innate immune cells express a diverse array of chemokines, cytokines, growth factors, lipid mediators, and oxidative products, with wide-ranging effects on tissue repair, inflammation, and adaptive immunity. During steady state, innate immunity restricts maladaptive activation of the adaptive immune system, but during disease, it activates and targets the adaptive response to the insult. In this chapter, we will focus on the role of the innate immune response and implications for health and cardiovascular disease.

During steady-state conditions, granulocytes in the heart are rare. However, following injury, eosinophils, basophils, and mast cells infiltrate the heart. Following myocardial infarction, eosinophils are recruited to the heart in both clinical and experimental models [2, 3]. Genetic depletion of eosinophils in murine models resulted in a reduction of CD206 reparative macrophages (possibly through inter-leukin (IL)-4 signaling) and subsequent adverse remodeling [2, 3], implicating a role for eosinophils conferring protection following myocardial infarction. Opposingly, eosinophils are also associated with heart failure [3]. In a cohort of patients with symptomatic heart failure, Heat2, a long, noncoding RNA, was significantly upregulated [4]. Heat2 is expressed in both eosinophils and basophils and modulates the proliferation, adhesion, invasion, and transmigration of eosinophils and basophils into the heart in the setting of heart failure [4]. Mast cells, another granulocyte, release cytokines (such as tumor necrosis factor (TNF)) that promote myocardial fibrosis and lead to adverse cardiac remodeling after myocardial infarction [5–8]. Genetic depletion of mast cells or mast cell stabilization showed improved outcomes after myocardial injury [9]. Last, neutrophils respond to pro-inflammatory cytokines and chemokines and are recruited to the heart following injury. Heart-resident macrophages can promote recruitment of neutrophils [6]. In summary, the granulocytes are early innate immune response elements that play important roles in the pathogenesis of disease after cardiac injury. They play independent roles as well as integrative roles with other innate immune cells: the monocytes, macrophages, and dendritic cells. We will focus on these three cell populations for the remainder of the chapter.