Signaling pathway for phagocyte priming upon encounter with apoptotic cells

Abstract

The phagocytic elimination of cells undergoing apoptosis is an evolutionarily conserved innate immune mechanism for eliminating unnecessary cells. Previous studies showed an increase in the level of engulfment receptors in phagocytes after the phagocytosis of apoptotic cells, which leads to the enhancement of their phagocytic activity. However, precise mechanisms underlying this phenomenon require further clarification. We found that the pre-incubation of a phagocyte cell line with the fragments of apoptotic cells enhanced the subsequent phagocytosis of apoptotic cells, accompanied by an augmented expression of the engulfment receptors Draper and integrin αPS3. The DNA-binding activity of the transcription repressor Tailless was transiently raised in those phagocytes, depending on two partially overlapping signal-transduction pathways for the induction of phagocytosis as well as the occurrence of engulfment. The RNAi knockdown of in phagocytes abrogated the enhancement of both phagocytosis and engulfment receptor expression. Furthermore, the hemocyte-specific RNAi of reduced apoptotic cell clearance in embryos. Taken together, we propose the following mechanism for the activation of phagocytes after an encounter with apoptotic cells: two partially overlapping signal-transduction pathways for phagocytosis are initiated; transcription repressor Tailless is activated; expression of engulfment receptors is stimulated; and phagocytic activity is enhanced. This phenomenon most likely ensures the phagocytic elimination of apoptotic cells by stimulated phagocytes and is thus considered as a mechanism to prime phagocytes in innate immunity.

Protein S and Gas6 induce efferocytosis of HIV-1-infected cells

“…Thus, efferocytosis of dead or late apoptotic virus-infected cells will be able to inhibit production of such non-enveloped viruses. Indeed, efferocytosis has been shown to inhibit replication of a non-enveloped virus, Drosophila C, both in vitro and in vivo (Nainu et al, 2015; Nonaka et al, 2017). …”

“…Viral infection induces changes of cell surface molecules related to cell death, and macrophages can recognize these changes and engulf the affected cells. It has been reported that macrophages perform efferocytosis of cells infected with the influenza (Fujimoto et al, 2000; Hashimoto et al, 2007; Shiratsuchi et al, 2000; Watanabe et al, 2005, 2002, 2004; Mukherjee et al, 2017), papilloma (Hermetet et al, 2016), and Drosophila C viruses (Nainu et al, 2015; Nonaka et al, 2017), as well as Lymphocytic choriomeningitis virus (LCMV) (Alatery et al, 2010), and Human Immunodeficiency Virus Type 1 (HIV-1) (Akbar et al, 1994). …”

Protective effects of <i>Phaseolus vulgaris</i> lectin against viral infection in <i>Drosophila </i>

“…The mRNA levels of various antimicrobial peptides, the Toll pathway-induced attacin and diptericin as well as the Imd pathway-induced defensin, drosomycin, and metchnikowin (10), were determined, and we found that the mRNA levels of some antimicrobial peptides, such as diptericin and defensin, marginally increased in flies after feeding with PHA-L4 ( Figure 6A). We then similarly analyzed the mRNAs of Draper and integrin αPS3-βν, engulfment receptors that activate two partly overlapping signaling pathways for the induction of phagocytosis of apoptotic cells by Drosophila hemocytes (21). The data indicated a dramatic increase in the levels of the mRNAs of both Draper and integrin βν in flies after lectin feeding ( Figure 6B): signals derived from the mRNA of integrin αPS3 were not detected under the conditions adopted in this study (data not shown).…”

Simu-dependent clearance of dying cells regulates macrophage function and inflammation resolution

“…57,58 Nonetheless, clearance of apoptotic cells is associated with increased expression of phagocytic receptors in a number of phagocytic cell types, including macrophages. 12,[59][60][61] Drosophila embryonic macrophages also undergo remarkable shifts in behavior over the fly life cycle, controlled in part by lipid hormone signalling. 62,63 However, the anti-inflammatory phenotype associated with acute induction of apoptosis would necessitate rapid reprogramming, unlikely for lipid hormone signalling, suggesting a more rapid mechanism, such as release of find-me cues.…”