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| Open AccessPhagosomal signalling of the C-type lectin receptor Dectin-1 is terminated by intramembrane proteolysis
Dectin-1 is a critical component of the innate sensing repertoire which is involved in pattern based recognition of fungal pathogens. Here the authors show that intramembrane proteolysis is involved in the regulation of the antifungal host response by termination of the phagosomal signalling of Dectin-1.
- Torben Mentrup
- , Anna Yamina Stumpff-Niggemann
- & Bernd Schröder
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Article
| Open AccessSalmonella effector SopD promotes plasma membrane scission by inhibiting Rab10
Salmonella secretes the effector protein SopD into the host cell cytoplasm, leading to scission of the plasma membrane through unclear mechanisms. Here, Boddy et al. show that SopD binds to and inhibits the small GTPase Rab10, thus promoting removal of Rab10 and recruitment of dynamin-2 to drive plasma membrane scission.
- Kirsten C. Boddy
- , Hongxian Zhu
- & John H. Brumell
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| Open AccessOxidation inhibits autophagy protein deconjugation from phagosomes to sustain MHC class II restricted antigen presentation
LC3-associated phagocytosis (LAP) is a non-canonical use of the autophagy machinery that can contribute to immune responses. Here, the authors describe the mechanism by which ROS production regulates LAPosome stabilization sustaining MHC II dependent antigen presentation.
- Laure-Anne Ligeon
- , Maria Pena-Francesch
- & Christian Münz
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| Open AccessCrbn modulates calcium influx by regulating Orai1 during efferocytosis
Calcium flux must be carefully controlled during the phagocytosis of apoptotic cells (efferocytosis), although how this occurs is not fully understood. Here, the authors show that the Cereblon E3 ligase regulates Orai1 degradation and subsequently SOCE-mediated calcium influx.
- Hyunji Moon
- , Chanhyuk Min
- & Daeho Park
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Article
| Open AccessAcid ceramidase of macrophages traps herpes simplex virus in multivesicular bodies and protects from severe disease
Macrophages are critical in limiting replication of herpes simplex virus type 1 (HSV-1). Here the authors show how acid ceramidase and its enzymatic product sphingosine enable multivesicular bodies to function as an anti-viral mechanism.
- Judith Lang
- , Patrick Bohn
- & Karl S. Lang
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Article
| Open AccessA phosphatidylinositol 4,5-bisphosphate redistribution-based sensing mechanism initiates a phagocytosis programing
The origin of Fc receptor-based phagocytosis is unknown, although plasma lipid redistribution after solid structure binding induces similar phagocytic signaling. Here, Mu et al. show that PIP2 accumulation from plasma membrane deformation recruits Moesin to trigger receptor-independent phagocytosis.
- Libing Mu
- , Zhongyuan Tu
- & Yan Shi
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Article
| Open AccessAlveolar macrophages are critical for broadly-reactive antibody-mediated protection against influenza A virus in mice
Broadly reactive antibodies that recognize influenza A virus HA can be protective, but the mechanism is not completely understood. Here, He et al. show that the inflammatory response and phagocytosis mediated by the interaction between protective antibodies and macrophages are essential for protection.
- Wenqian He
- , Chi-Jene Chen
- & Gene S. Tan
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| Open AccessPhagocyte respiratory burst activates macrophage erythropoietin signalling to promote acute inflammation resolution
Hypoxia induced during inflammation promotes the resolution phase. Here the authors show that the hypoxia results from the respiratory burst in myeloid cells, and induces local EPO production and signaling, which enhances macrophage phagocytosis of debris and migration to draining lymph nodes to promote resolution.
- Bangwei Luo
- , Jinsong Wang
- & Zhiren Zhang
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Article
| Open AccessPhosphoinositide 3-kinase enables phagocytosis of large particles by terminating actin assembly through Rac/Cdc42 GTPase-activating proteins
Phagocytosis of large (but not small) particles requires PI 3-kinase activity. Here, Schlam et al. show that Rho GTPase-activating proteins are recruited to the phagocytic cup by products of PI 3-kinase, resulting in the local inactivation of Rac and Cdc42 and allowing for the completion of internalization of large particles.
- Daniel Schlam
- , Richard D. Bagshaw
- & Sergio Grinstein
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Article
| Open AccessCell migration and antigen capture are antagonistic processes coupled by myosin II in dendritic cells
Dendritic cells alternate between fast and slow migratory behaviours, however in the absence of a component of the antigen processing machinery, migration is uniform and fast. Chabaudet al. now show that slow migration results from the relocalisation of myosin II to the cell front where it promotes antigen capture.
- Mélanie Chabaud
- , Mélina L. Heuzé
- & Ana-Maria Lennon-Duménil
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The matricellular protein CCN1 mediates neutrophil efferocytosis in cutaneous wound healing
Neutrophils are the first line of response to injury but their persistence can inhibit the resolution phase of tissue repair. Here the authors show that an extracellular matrix protein promotes neutrophil clearance by macrophages, serving as a bridge between the two cell types and speeding up tissue repair.
- Joon-Il Jun
- , Ki-Hyun Kim
- & Lester F. Lau
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Prion-like transmission of neuronal huntingtin aggregates to phagocytic glia in the Drosophila brain
Phagocytic glia can internalize protein aggregates in vitro. Here Pearce et al. show in Drosophila that glia clear mutant huntingtin (Htt) aggregates in a scavenger receptor Draper-dependent manner in vivo, and that internalized Htt aggregates induce the prion-like conversion of wild-type Htt expressed in the glial cytoplasm.
- Margaret M. P. Pearce
- , Ellen J. Spartz
- & Ron R. Kopito
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HIV-1 Tat inhibits phagocytosis by preventing the recruitment of Cdc42 to the phagocytic cup
Phagocytic activity of macrophages is reduced in HIV-1-infected patients, but the reason for this is unknown. Here, the authors report that secreted Tat protein inhibits phagocytosis by binding to the phospholipid PI(4,5)P2and impairing the recruitment of small GTPase Cdc42 to the phagocytic cup.
- Solène Debaisieux
- , Simon Lachambre
- & Bruno Beaumelle
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p85α recruitment by the CD300f phosphatidylserine receptor mediates apoptotic cell clearance required for autoimmunity suppression
Apoptotic cell clearance is important for the maintenance of immune homeostasis. Here, Tian et al. reveal how a phosphatidylserine (PS) receptor participates in the clearance of apoptotic cells, and show that loss of the receptor can lead to autoimmunity.
- Linjie Tian
- , Seung-Chul Choi
- & John E. Coligan
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Caspase-mediated activation of Caenorhabditis elegans CED-8 promotes apoptosis and phosphatidylserine externalization
As they die, apoptotic cells present phosphatidylserine on the outer leaflet of the plasma membrane, which serves as an ‘eat-me’ signal for nearby phagocytes. Chen et al. identify the caspase substrate CED-8 as a key regulator of phosphatidylserine externalization during apoptosis in C. elegans.
- Yu-Zen Chen
- , James Mapes
- & Ding Xue
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Annexin A2 binds to endosomes following organelle destabilization by particulate wear debris
Endosomes contain hydrolytic enzymes, and recent reports have suggested that the endosomal membrane can be damaged by wear particles, resulting in the release of their contents and an inflammatory response. In this study, a role for annexin II in the repair of the damaged endosome membrane is reported.
- Brian Scharf
- , Cristina C. Clement
- & Laura Santambrogio
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A C2 domain protein kinase initiates phagocytosis in the protozoan parasite Entamoeba histolytica
The phagocytosis of bacteria and other cells by trophozoites is an important process required for nutrition and pathogenesis. The authors identify a kinase, EhC2PK, that binds to the calcium-binding protein, EhCaBP1, and find that both proteins are involved in phagocytosis by the parasiteEntamoeba histolytica.
- Somlata
- , Sudha Bhattacharya
- & Alok Bhattacharya