The life cycle of phagosomes: formation, maturation, and resolution

Levin, Roni; Grinstein, Sergio; Canton, Johnathan

doi:10.1111/imr.12439

Cited by 250 publications

(349 citation statements)

References 288 publications

(331 reference statements)

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“…Furthermore, phagocytosis is an essential defense mechanism of innate immunity, by recognizing, engulfing and destroying invading microbes. Professional phagocytes, such as neutrophils, dendritic cells (DCs), monocytes, and macrophages (MΦs), have different phagocytic capacities 3, 4. However, epithelial cells, fibroblasts, and certain B lymphocyte subsets also engage in phagocytosis 5, 6, 7.…”

Section: Phagosome Maturation In the Context Of Inflammation And Infementioning

confidence: 99%

Patterns, Receptors, and Signals: Regulation of Phagosome Maturation

Pauwels

Trost

Beyaert

et al. 2017

Trends in Immunology

211

177

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Recognition of microbial pathogens and dead cells and their phagocytic uptake by specialized immune cells are essential to maintain host homeostasis. Phagosomes undergo fusion and fission events with endosomal and lysosomal compartments, a process called ‘phagosome maturation’, which leads to the degradation of the phagosomal content. However, many phagocytic cells also act as antigen-presenting cells and must balance degradation and peptide preservation. Emerging evidence indicates that receptor engagement by phagosomal cargo, as well as inflammatory mediators and cellular activation affect many aspects of phagosome maturation. Unsurprisingly, pathogens have developed strategies to hijack this machinery, thereby interfering with host immunity. Here, we highlight progress in this field, summarize findings on the impact of immune signals, and discuss consequences for pathogen elimination.

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Section: Phagosome Maturation In the Context Of Inflammation And Infementioning

confidence: 99%

Patterns, Receptors, and Signals: Regulation of Phagosome Maturation

Pauwels

Trost

Beyaert

et al. 2017

Trends in Immunology

211

177

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“…That the N-and C-terminal regions of TRPM2 did not face the outer side of phagosomes suggests that phagosomal TRPM2 did not originate from the plasma membrane after phagocytosis. Phagosomal maturation requires spatial and temporal orchestration of proteins (for a review, see Levin et al, 2016). During the formation of phagosomes, proteins such as transferrin receptor are shuttled back to the plasma membrane whereas proteins such as the GTPase Rab5 are recruited into phagosomes (Levin et al, 2016).…”

Section: (Knowles Et Al 2011) the Trpm2mentioning

confidence: 99%

“…Phagosomal maturation requires spatial and temporal orchestration of proteins (for a review, see Levin et al, 2016). During the formation of phagosomes, proteins such as transferrin receptor are shuttled back to the plasma membrane whereas proteins such as the GTPase Rab5 are recruited into phagosomes (Levin et al, 2016). Other phagosomal proteins undergo retrograde traffic to the trans-Golgi network via tubulovesicular structures (Levin et al, 2016).…”

Section: (Knowles Et Al 2011) the Trpm2mentioning

confidence: 99%

“…During the formation of phagosomes, proteins such as transferrin receptor are shuttled back to the plasma membrane whereas proteins such as the GTPase Rab5 are recruited into phagosomes (Levin et al, 2016). Other phagosomal proteins undergo retrograde traffic to the trans-Golgi network via tubulovesicular structures (Levin et al, 2016). The mechanism of TRPM2 positioning in phagosomes is not known.…”

Section: (Knowles Et Al 2011) the Trpm2mentioning

confidence: 99%

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Role of the phagosomal redox-sensitive TRP channel TRPM2 in regulating bactericidal activity of macrophages

Kiya

Gong

et al. 2017

Journal of Cell Science

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Acidification of macrophage phagosomes serves an important bactericidal function. We show here that the redox-sensitive transient receptor potential (TRP) cation channel TRPM2 is expressed in the phagosomal membrane and regulates macrophage bactericidal activity through the activation of phagosomal acidification. Measurement of the TRPM2 current in phagosomes identified TRPM2 as a functional redox-sensitive cation channel localized in the phagosomal membrane. Simultaneous measurements of phagosomal Ca 2+ changes and phagosome acidification in macrophages undergoing phagocytosis demonstrated that TRPM2 was required to mediate the efflux of cations and for phagosomal acidification during the process of phagosome maturation. Acidification in phagosomes was significantly reduced in macrophages isolated from Trpm2 −/− mice as compared to wild type, and acidification was coupled to reduced bacterial clearance in Trpm2 −/− mice. Trpm2 +/+ macrophages treated with the vacuolar H + -ATPase inhibitor bafilomycin showed reduced bacterial clearance, similar to that in Trpm2 −/− macrophages. Direct activation of TRPM2 using adenosine diphosphate ribose (ADPR) induced both phagosomal acidification and bacterial killing. These data collectively demonstrate that TRPM2 regulates phagosomal acidification, and is essential for the bacterial killing function of macrophages.

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“…Phagocytosis and macropinocytosis are actin-driven processes that entail rearrangements of the plasma membrane to engulf extracellular material, followed by delivery of the ingested material into lysosomes for extraction of nutrients (6). Morphologically, several stages can be distinguished, starting with the initiation of cup formation after detection of external cues via diverse G proteincoupled receptors, such as the Fc-γ and C3a receptors in mammalian cells (7), followed by membrane protrusion and the pursestring-like closure of the cup leading to the separation of the closed vesicle from the plasma membrane (6,8).…”

mentioning

confidence: 99%

ADiaphanous-related formin links Ras signaling directly to actin assembly in macropinocytosis and phagocytosis

Junemann

Filić

Winterhoff

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

101

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SignificanceMacropinocytosis and phagocytosis are two Ras-regulated, highly related processes of great physiological relevance collectively termed large-scale endocytosis. Both are actin-driven and entail engulfment of extracellular material by crown-like protrusions. Aside from the Arp2/3 complex, which serves as the main nucleator of branched actin filaments at the cup rim, the underlying mechanisms of actin assembly still remain elusive. Here, we analyzed the role of Diaphanous-related formin G (ForG) from Dictyostelium by biochemical, genetic, and imaging techniques. Our data demonstrate that this formin exhibits a rather weak nucleation activity and imply that ForG-mediated filament elongation synergizes with the Arp2/3 complex in actin assembly. Finally, we identify ForG as a Ras-regulated formin and show its significance for actin assembly in endocytic structures.

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The life cycle of phagosomes: formation, maturation, and resolution

Cited by 250 publications

References 288 publications

Patterns, Receptors, and Signals: Regulation of Phagosome Maturation

Patterns, Receptors, and Signals: Regulation of Phagosome Maturation

Role of the phagosomal redox-sensitive TRP channel TRPM2 in regulating bactericidal activity of macrophages

ADiaphanous-related formin links Ras signaling directly to actin assembly in macropinocytosis and phagocytosis

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