Table 1.
Impacts of autophagy and LAP on antifungal immunity.
| Approaches | Findings | Reference | |
|---|---|---|---|
| A. fumigatus |
• Rubicon-, Cybb-, Atg4b-, or Ulk1-deficient mice • Atg3fl/flLysM-Cre mice, Atg5fl/flLysM-Cre mice, Atg7fl/flLysM-Cre mice, Atg12fl/flLysM-Cre mice, Atg14fl/flLysM-Cre mice, Becn1fl/flLysM-Cre mice, Rb1cc1fl/flLysM-Cre mice • shRNA for Rubicon • 3-MA • Rapamycin |
• A. fumigatus phagocytosed by macrophages induces LAP formation • LAP, but not canonical autophagy, is required for clearance of A. fumigatus in vitro and in vivo. • Lack of LAP enhances fungi-induced pulmonary inflammation and granulomas • SNP in Atg16L does not affect LAP formation |
(33) |
| • 3-MA • Chloroquine |
• Autophagy suppresses inflammasome-mediated inflammation during A. fumigatus infection • IL-1R blockade restores autophagy and suppresses fungal growth in CGD mice. |
(58) | |
| C. neoformans | • RNAi screening • siRNA for Atg2a, Atg5, Atg9, Atg12, and Map1lc3a (Coding LC3) • 3-MA |
• Knockdown of Atg5, Atg9a, and Atg12 decreases phagocytosis of C. neoformans by macrophages • Knockdown of Atg2a, Atg5, Atg9a, Atg12, and LC3 decreases fungal replication and escape of C. neoformans • Autophagy inhibition by 3-MA reduces phagocytosis, fungal replication, and escape of C. neoformans |
(54) |
| • shRNA for Atg5 • Atg5fl/flLysM-Cre mice |
• Phagocytosed C. neoformans are surrounded by LAP in macrophages • Atg5-knock down by shRNA does not affect phagocytosis • Atg5-knock down by shRNA or Atg5-knock-out decreases fungicidal activity in macrophages |
(50) | |
| C. albicans | • shRNA for Atg5 • Atg5fl/flLysM-Cre mice |
• Phagocytosed C. albicans are surrounded by LC3 in macrophages • Atg5-knockdown decreases phagocytosis and fungicidal activity of macrophages in vitro • Lack of ATG5 in myeloid cells enhances susceptibility of mice against systemic C. albicans infection |
(50) |
|
• Atg7fl/flLysM-Cre mice • 3-MA • Cohort study of candidemia patients |
• Lack of ATG7 in myeloid cells does not impact on susceptibility of mice against systemic C. albicans infection • Autophagy inhibition by 3-MA does not affect phagocytosis and fungicidal activity against C. albicans in human monocytes • SNP in autophagy-related genes does not associate with incidence of candidemia |
(44) | |
|
• Atg7fl/flLysM-Cre mice • 3-MA • Rapamycin |
• C. albicans induces autophagy in macrophages enhances susceptibility against systemic C. albicans infection • Phagocytosed C. albicans are not surrounded by LC3 • Autophagy does not affect phagocytosis and fungicidal activity of macrophages and neutrophils • Autophagic sequestration of A20 enhances NFκB-mediated chemokine production in tissue-resident macrophages and increases neutrophil recruitment to infected site • Lack of autophagy in myeloid cells |
(43) | |
| • In vivo imaging using zebra fish | • Very few LC3+ phagosome contain C. albicans in vivo | (46) | |
| • LC3-deficient BMMs | • Dectin-1-induced signaling triggers LAP formation in macrophages • HK C. albicans induces LAP in macrophages • Live C. albicans induces modest level of LAP in macrophages • LC3-deficiency decreases fungicidal activity of macrophages against C. albicans |
(45) |