Autophagy proteins stabilize pathogen-containing phagosomes for prolonged MHC II antigen processing

Romão, Susana; Gasser, Nathalie; Becker, Andrea C.; Guhl, Bruno; Bajagic, Milica; Ziegler, Urs; Roesler, Joachim; Dengjel, Jörn; Reichenbach, Janine; Münz, Christian

doi:10.1084/jem.21013oia64

Cited by 40 publications

(76 citation statements)

References 16 publications

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“…Several groups have provided evidence that the lipidation of LC3 onto phagosomes or entotic vacuoles in macrophages and epithelial cells promotes lysosome fusion and the degradation of engulfed extracellular cargo (62,118), which would be predicted to promote amino acid scavenging by macropinocytosis. However, a recent report concluded that LC3 may delay lysosome fusion in dendritic cells (119). The more precise function of lipidated LC3 at these non-autophagosomal endocytic play important roles in normal physiology.…”

Section: Autophagy or Autophagy Proteins?mentioning

confidence: 99%

Autophagy in cellular metabolism and cancer

Jiang¹,

Overholtzer²,

Thompson³

2015

J. Clin. Invest.

180

146

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Section: Autophagy or Autophagy Proteins?mentioning

confidence: 99%

Autophagy in cellular metabolism and cancer

Jiang¹,

Overholtzer²,

Thompson³

2015

J. Clin. Invest.

180

146

View full text Add to dashboard Cite

“…We previously showed that ROS production by the CYBB NADPH oxidase is required for LC3 recruitment to phagosomes, 5 an observation confirmed by others. 6,10 In the present study we examined phagosome maturation in the absence of CYBB-dependent ROS production. Despite the fact that CYBB is required for LAP, 5,6,10 OpZ phagosomes matured faster in the absence of intraphagosomal ROS than in the WT counterparts (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…4,6 LC3 conjugation to a phagosome is observed in hematopoietic cell types, including macrophages, dendritic cells, and neutrophils. [4][5][6][7][8][9][10][11][12] It has also been observed in retinal pigment epithelial cells, 13,14 which are macrophage-like and expresses some hematopoietic markers. 15 The role of LAP in nonhematopoietic cell types is not yet clear.…”

Section: Introductionmentioning

confidence: 99%

“…5,7 LAP is triggered in response to particles that stimulate TLRs, FCGR2A/FcgR2A, CLEC7A/dectin-1, and other cargo such as apoptotic and entotic cells. [4][5][6][7][8][9][10] In addition to ROS, LAP requires a subset of autophagy components, such as ATG5, ATG7, ATG12, ATG16L1, BECN1/Beclin 1, and PIK3C3/VPS34, whereas others, such as ULK1 (unc51-like kinase 1), ATG13, and RB1CC1/FIP200 are dispensable. 4,6 LC3 conjugation to a phagosome is observed in hematopoietic cell types, including macrophages, dendritic cells, and neutrophils.…”

Section: Introductionmentioning

confidence: 99%

“…4 However, a study in human macrophages observed quite the opposite-LC3 recruitment to zymosan-containing phagosomes was associated with delayed phagosomal fusion with the lysosome. 10 Therefore, the impact of LC3 recruitment to phagosomes remains unclear. Hence, we explored how the phagosome maturation is affected in the absence of ATG proteins.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Autophagy proteins are not universally required for phagosome maturation

2016

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Phagocytosis plays a central role in immunity and tissue homeostasis. After internalization of cargo into single-membrane phagosomes, these compartments undergo a maturation sequences that terminates in lysosome fusion and cargo degradation. Components of the autophagy pathway have recently been linked to phagosome maturation in a process called LC3-associated phagocytosis (LAP). In this process, autophagy machinery is thought to conjugate LC3 directly onto the phagosomal membrane to promote lysosome fusion. However, a recent study has suggested that ATG proteins may in fact impair phagosome maturation to promote antigen presentation. Here, we examined the impact of ATG proteins on phagosome maturation in murine cells using FCGR2A/FcgR-dependent phagocytosis as a model. We show that phagosome maturation is not affected in Atg5-deficient mouse embryonic fibroblasts, or in Atg5-or Atg7-deficient bone marrow-derived macrophages using standard assays of phagosome maturation. We propose that ATG proteins may be required for phagosome maturation under some conditions, but are not universally required for this process.

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Novel and conventional inhibitors of canonical autophagy differently affect LC3‐associated phagocytosis

et al. 2022

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In autophagy, LC3-positive autophagophores fuse and encapsulate the autophagic cargo in a double-membrane structure. In contrast, lipidated LC3 (LC3-II) is directly formed at the phagosomal membrane in LC3-associated phagocytosis (LAP). In this study, we dissected the effects of autophagy inhibitors on LAP. SAR405, an inhibitor of VPS34, reduced levels of LC3-II and inhibited LAP. In contrast, the inhibitors of endosomal acidification bafilomycin A1 and chloroquine increased levels of LC3-II, due to reduced degradation in acidic lysosomes. However, while bafilomycin A1 inhibited LAP, chloroquine did not. Finally, EACC, which inhibits the fusion of autophagosomes with lysosomes, promoted LC3 degradation possibly by the proteasome. Targeting LAP with small molecule inhibitors is important given its emerging role in infectious and autoimmune diseases.

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Autophagy proteins stabilize pathogen-containing phagosomes for prolonged MHC II antigen processing

Cited by 40 publications

References 16 publications

Autophagy in cellular metabolism and cancer

Autophagy in cellular metabolism and cancer

Autophagy proteins are not universally required for phagosome maturation

Novel and conventional inhibitors of canonical autophagy differently affect LC3‐associated phagocytosis

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