Monocyte trafficking in acute and chronic inflammation

Abstract

Environmental signals at the site of inflammation mediate rapid monocyte mobilization and dictate differentiation programs whereby these cells give rise to macrophages or dendritic cells. Monocytes participate in tissue healing, clearance of pathogens and dead cells, and initiation of adaptive immunity. However, recruited monocytes can also contribute to the pathogenesis of infection and chronic inflammatory disease, such as atherosclerosis. Here, we explore monocyte trafficking in the context of acute inflammation, relying predominantly on data from microbial infection models. These mechanisms will be compared to monocyte trafficking during chronic inflammation in experimental models of atherosclerosis. Recent developments suggest that monocyte trafficking shares common themes in diverse inflammatory diseases; however, important differences exist between monocyte migratory pathways in acute and chronic inflammation.

Figure 1. Monocyte trafficking in acute injury or infection

(1) Signals including CCR2-ligand (CCL2 and CCL7) binding induce classical monocyte egress from bone marrow during inflammation or infection [32]. (2) Angiotensin II induces monocyte egress from the splenic reservoir during myocardial infarction [9]. While an increase in total monocytes is observed in the blood concomitant with a decrease in splenic monocytes [9], it is not clear if nonclassical monocytes are released from the spleen during myocardial infarction. (3) Classical monocytes arrive first at the injured heart, followed by non-classical monocytes [19]. Only classical monocytes are recruited to injured or infected sites such as brain, gut, liver and kidney. (4) Upon recruitment, monocytes may differentiate into macrophages, dendritic cells, or TipDCs.

Figure 2. Monocyte recruitment during in atherosclerosis

During progressive disease, both classical and nonclassical monocytes are recruited to sites of activated endothelium through CCR2, CCR5, and CX3CR1 signaling pathways [67]. Monocytes accumulate in the intima, take up lipid (yellow dots), and develop into lipid-laden foam cells. During regressive disease, recruitment of both subsets is reduced [72]. In contrast to the acute injured heart model, where recruited nonclassical monocytes contribute to tissue healing [19], in atherosclerosis, healing is correlated with a reduction in total monocyte recruitment.