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Abstract
SummaryMacrophages must not only be responsive to an array of different stimuli, such as infection and cellular damage, but also perform phagocytosis within the diverse and complex tissue environments found in vivo. This requires a high degree of morphological and therefore cytoskeletal plasticity. Here, we use the exceptional genetics and in vivo imaging of Drosophila embryos to study macrophage phagocytic versatility during apoptotic corpse clearance. We find that macrophage phagocytosis is highly robust, arising from their possession of two distinct modes of engulfment that utilize exclusive suites of actin-regulatory proteins. “Lamellipodial phagocytosis” is Arp2/3-complex-dependent and allows cells to migrate toward and envelop apoptotic corpses. Alternatively, Diaphanous and Ena drive filopodial phagocytosis to reach out and draw in debris. Macrophages switch to “filopodial phagocytosis” to overcome spatial constraint, providing the robust plasticity necessary to ensure that whatever obstacle they encounter in vivo, they fulfil their critical clearance function.
Highlights
Macrophages are highly motile and phagocytic cells that are actively recruited to clear infections and debris arising from development and tissue homeostasis or damage
We have demonstrated that lamellipodial phagocytosis is strongly suppressed in scar or arp3 mutant macrophages, which instead switch to filopodial phagocytosis (Figures 2B, 2C, and 2F)
We have demonstrated that macrophages utilize Dia and/or Ena to extend phagocytic filopods to overcome the loss of the Arp2/3 complex and the associated loss of lamellipods and motility
Summary
Macrophages are highly motile and phagocytic cells that are actively recruited to clear infections and debris arising from development and tissue homeostasis or damage. These professional phagocytes dynamically alter their actin cytoskeleton to drive both their migration toward and engulfment of material. These cytoskeletal rearrangements are coordinated by highly conserved actin regulators. Foremost among these is the Arp2/ 3 complex, which generates branched actin meshes vital for extending large protrusions such as lamellipods (Mullins et al, 1998; Svitkina and Borisy, 1999). We demonstrate that in vivo, macrophages resort to filopodial phagocytosis to overcome spatial constriction and reduced mobility so as to maintain their critical clearance function under all circumstances
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