Autophagy Protects against Eosinophil Cytolysis and Release of DNA

Abstract

The presence of eosinophils in the airway is associated with asthma severity and risk of exacerbations. Eosinophils deposit their damaging products in airway tissue, likely by degranulation and cytolysis. We previously showed that priming blood eosinophils with IL3 strongly increased their cytolysis on aggregated IgG. Conversely, IL5 priming did not result in significant eosinophil cytolysis in the same condition. Therefore, to identify critical events protecting eosinophils from cell cytolysis, we examined the differential intracellular events between IL5- and IL3-primed eosinophils interacting with IgG. We showed that both IL3 and IL5 priming increased the eosinophil adhesion to IgG, phosphorylation of p38, and production of reactive oxygen species (ROS), and decreased the phosphorylation of cofilin. However, autophagic flux as measured by the quantification of SQSTM1-p62 and lipidated-MAP1L3CB over time on IgG, with or without bafilomycin-A1, was higher in IL5-primed compared to IL3-primed eosinophils. In addition, treatment with bafilomycin-A1, an inhibitor of granule acidification and autophagolysosome formation, enhanced eosinophil cytolysis and DNA trap formation in IL5-primed eosinophils. Therefore, this study suggests that increased autophagy in eosinophils protects from cytolysis and the release of DNA, and thus limits the discharge of damaging intracellular eosinophilic contents.

Comparison with gastric cancer-associated genes reveals the role of ferroptosis-related genes in eosinophils of asthma patients: A bioinformatic study

“…It is supported by the report that IL-5 and interleukin-3 priming increased ROS production in eosinophils. [69] To explore the regulation of FerrDEGs expression in eosinophils, we constructed a LncRNA-mediated ceRNA network involving SNHG5/MIR193B/PTEN ceRNA pathway. We found that PTEN was decreased in eosinophils, which is consistent with the finding of Kwak et al and Tetsuya et al [70,71] PTEN was the fourth of the top 10 hub genes in exclusive FerrDEGs and original FerrDEGs.…”

“…It is supported by the report that IL-5 and interleukin-3 priming increased ROS production in eosinophils. [ 69 ]…”

Eosinophils from A to Z

“…100 Surprisingly, the absence of ATG5/Atg5 was shown to increase eosinophil effector functions such as degranulation, eosinophil extracellular trap (EET) formation, and bacterial clearance (see "Host defense"). 101 Moreover, a recent study reported a protective effect of autophagy against cytolysis of mature eosinophils in humans 102 (see "Degranulation").…”

Galectin-10 as a Potential Biomarker for Eosinophilic Diseases

“…In the in vitro experimental setting, human eosinophils undergo cytolysis/ETosis by various stimuli, such as calcium ionophore, phorbol 12-myristate 13-acetate, IL-5/granulocyte macrophage colony-stimulating factor with platelet-activating factor, immobilized or aggregated Igs, autoantibodies, and fungi [ 57 , 60 , 61 , 62 , 63 , 64 ]. Eosinophil ETosis (EETosis) has been implicated in a wide range of eosinophilic diseases, such as asthma [ 65 , 66 ], allergic bronchopulmonary aspergillosis [ 67 , 68 ], eosinophilic otitis [ 61 , 69 ], eosinophilic chronic rhinosinusitis (chronic rhinosinusitis with nasal polyps) [ 61 ], hypereosinophilic syndrome [ 36 , 57 , 70 ], Wells syndrome (eosinophilic cellulitis) [ 71 ], eosinophilic granulomatosis with polyangiitis ([EGPA] Churg–Strauss syndrome) [ 72 , 73 ], eosinophilic pneumonia [ 74 , 75 , 76 ], ulcerative colitis [ 59 ], and chronic obstructive pulmonary diseases [ 77 ].…”