Abstract

For half of a century, it has been known that non-professional phagocytes, such as fibroblasts, endothelial, and epithelial cells, are capable of efferocytosis (engulfment of apoptotic cells). Non-professional phagocytes differ from professional phagocytes in the range and efficiency of engulfment. Much of the recognition and underlying signaling machinery between non-professional and professional phagocytes is the same, but it is not known how the engulfment capacity of non-professional phagocytes is controlled. Moreover, the signaling networks involved in cell corpse recognition, engulfment, and phagosome maturation are only partially understood. The Drosophila ovary provides an excellent system to investigate the regulation of phagocytic activity by epithelial cells, a major class of non-professional phagocytes. During Drosophila oogenesis, mid-stage egg chambers undergo apoptosis of the germline in response to nutrient deprivation. Epithelial follicle cells then undergo major cell shape changes and concomitantly engulf the germline material. Our previous work has established that Draper and the integrin α-PS3/β-PS heterodimer are required in follicle cells for germline cell clearance. In addition, we have characterized phagosome maturation pathways, and found that the JNK pathway amplifies the engulfment response. In this review, we discuss recent advances on the interplay between engulfment pathways in the follicular epithelium for cell clearance in the Drosophila ovary. We also provide a comparison to apoptotic cell clearance mechanisms in C. elegans and mammals, illustrating strong conservation of efferocytosis mechanisms by non-professional phagocytes.

Highlights

  • Apoptotic cell clearance by phagocytic cells is critical for organismal homeostasis

  • The anti-inflammatory cytokine containing multivesicular bodies (MVBs) suppress the expression of proinflammatory gene PTX3, suggesting a mechanism whereby macrophages signal to non-professional phagocytes to resolve inflammation [55]

  • Vitellogenesis begins at stage 8 of oogenesis, which has a characteristic loss of proportion between nurse cells and oocyte, where the oocyte becomes noticeably larger than the nurse cells

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Summary

Frontiers in Immunology

Received: 14 September 2017 Accepted: 09 November 2017 Published: 29 November 2017. Citation: Serizier SB and McCall K (2017) Scrambled Eggs: Apoptotic Cell Clearance by Non-Professional Phagocytes in the Drosophila Ovary. For half of a century, it has been known that non-professional phagocytes, such as fibroblasts, endothelial, and epithelial cells, are capable of efferocytosis (engulfment of apoptotic cells). The signaling networks involved in cell corpse recognition, engulfment, and phagosome maturation are only partially understood. The Drosophila ovary provides an excellent system to investigate the regulation of phagocytic activity by epithelial cells, a major class of non-professional phagocytes. Epithelial follicle cells undergo major cell shape changes and concomitantly engulf the germline material. We discuss recent advances on the interplay between engulfment pathways in the follicular epithelium for cell clearance in the Drosophila ovary. We provide a comparison to apoptotic cell clearance mechanisms in C. elegans and mammals, illustrating strong conservation of efferocytosis mechanisms by non-professional phagocytes

INTRODUCTION
APOPTOTIC CELL CLEARANCE
Adaptor proteins GTPases
PROFESSIONAL PHAGOCYTES IN
Hypodermal cells Gonadal sheath cells Pharyngeal muscle cells Endothelial cells
CHECKPOINTS OF CELL DEATH IN THE OVARY
CHARACTERIZATION OF ENGULFMENT BY EPITHELIAL FOLLICLE CELLS
APOPTOTIC CELL CLEARANCE IS AFFECTED BY CELL POLARITY
PHAGOSOME MATURATION IN THE Drosophila OVARY
DRAPER SIGNALS TO THE JNK SIGNALING PATHWAY IN MANY Drosophila TISSUES
ENGULFMENT ACROSS ORGANISMS
OPEN QUESTIONS IN THE FIELD ABOUT APOPTOTIC CELL CLEARANCE
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