Macrophage efferocytosis in health and disease

Abstract

Creating cellular homeostasis within a defined tissue typically relates to the processes of apoptosis and efferocytosis. A great example here is cell debris that must be removed to prevent unwanted inflammatory responses and then reduce autoimmunity. In view of that, defective efferocytosis is often assumed to be responsible for the improper clearance of apoptotic cells (ACs). This predicament triggers off inflammation and even results in disease development. Any disruption of phagocytic receptors, molecules as bridging groups, or signaling routes can also inhibit macrophage efferocytosis and lead to the impaired clearance of the apoptotic body. In this line, macrophages as professional phagocytic cells take the lead in the efferocytosis process. As well, insufficiency in macrophage efferocytosis facilitates the spread of a wide variety of diseases, including neurodegenerative diseases, kidney problems, types of cancer, asthma, and the like. Establishing the functions of macrophages in this respect can be thus useful in the treatment of many diseases. Against this background, this review aimed to recapitulate the knowledge about the mechanisms related to macrophage polarization under physiological or pathological conditions, and shed light on its interaction with efferocytosis.

Microplastics dysregulate innate immunity in the SARS-CoV-2 infected lung

“…4, Phagocytosis), and the increased proinflammatory responses (Fig. 4, Proinflammatory cytokines), might suggest increased secondary necrosis due to a reduction in the phagocytosis of apoptotic cells (efferocytosis) (Ge et al, 2022; Razi et al, 2023; Sachet et al, 2017). Multiple IPA Disease & Functions annotations suggest an increase in apoptosis signatures (Supplementary Table 6), with secondary necrosis known to be proinflammatory via secretion of a number of mediators such as HMGB1 and ATP (Sachet et al, 2017).…”

“…It is tempting to speculate that the ability of MPs to block efferocytosis via binding to the efferocytosis receptor Tim4 (Kuroiwa et al, 2023) provides a basis for understanding, at least some of the observations presented herein. Specifically, the clearly depressed phagocytosis signatures, the identification of multiple annotations associated with modulated macrophage responses (with macrophages the key mediators of efferocytosis), and the overall lack of detectable changes to adaptive immune responses, might be viewed as consistent with a role for dysregulated phagocytosis/efferocytosis (Ge et al, 2022; Razi et al, 2023). Reduced phagocytosis of SARS-CoV-2 infected cells at 2 dpi might reduce M1 macrophage activation, subsequent pDC activation (Garcia-Nicolas et al, 2023), and the ensuing cytokine responses (Severa et al, 2021; Van der Sluis et al, 2022).…”

Microplastics dysregulate innate immunity in the SARS-CoV-2 infected lung

“…The ability of MPs to block efferocytosis via binding to the efferocytosis receptor Tim4 ( 42 ), may provide a basis for understanding at least some of the transcriptional perturbation described herein. Specifically, the clearly depressed phagocytosis signatures, the identification of multiple annotations associated with modulation of macrophage responses (with macrophages the key mediators of efferocytosis), and the overall lack of detectable changes to adaptive immune responses, might be viewed as consistent with a role for dysregulated phagocytosis/efferocytosis ( 115 , 116 ). Reduced phagocytosis of SARS-CoV-2 infected cells at 2 dpi might reduce M1 macrophage activation, subsequent pDC activation ( 85 ), and the ensuing cytokine responses ( 86 , 136 ).…”

Mechanobiology of Ferroptotic Cancer Cells as a Novel “Eat‐Me” Signal: Regulating Efferocytosis through Layer‐by‐Layer Coating

“…[ 8 ] The failure or inadequate clearance of dead cells has been linked to several pathological conditions, including atherosclerosis, inflammation associated with aging, cancer, and infections. [ 9 ] The broad physiological and pathological implications of efferocytosis offer opportunities for targeted therapeutic interventions at various stages of the process to leverage the anti‐inflammatory benefits. However, the anti‐inflammatory features of tumor‐associated macrophages may pose challenges to effective antitumor responses.…”