Staphylococcal γ-hemolysins induce IL-4 production in murine basophils
Staphylococcal γ-hemolysins induce IL-4 production in murine basophils
复制标题
葡萄球菌 γ-溶血素诱导小鼠嗜碱性粒细胞产生 IL-4
DOI：
10.1016/j.bbrc.2022.09.070
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发表时间：
2022
影响因子：
3.1
通讯作者：
Hida S.
中科院分区：
文献类型：
--
作者：
Ogata A.;Hayashi K.;Kitano T.;Onozaki K.;Itoh S.;Hida S.
嗜碱性粒细胞可产生大量IL-4，参与2型炎症的发生和发展，并分泌α-溶血素、γ-溶血素和杀白细胞素等一系列致孔毒素。在这项研究中，我们研究了α-溶血素、γ-溶血素（HlgAB和HlgCB）和杀白细胞素（LukAB、LukED和Panton-Valentine杀白细胞素）对嗜碱性粒细胞功能的影响。除Panton-Valentine杀白细胞素外，所有成孔毒素均与小鼠骨髓源性嗜碱性粒细胞（BMB）结合。HlgAB和LukED在30 μg/ml的γ-溶血素、HlgAB和HlgCB诱导BMB释放乳酸脱氢酶，在3.3 μg/ml以上的γ-溶血素诱导BMB分泌IL-4，而其它毒素则不诱导BMB释放乳酸脱氢酶。LukAB不诱导，Hla和LukED仅诱导少量的IL-4。HlgBΔstem是HlgB茎区5个氨基酸的缺失突变体，可抑制HlgAB和HlgCB在BMB中的IL-4分泌。这些结果表明，细胞损伤和诱导IL-4在嗜碱性粒细胞由HlgAB需要孔的形成。在新鲜分离的鼠嗜碱性粒细胞中也观察到γ-溶血素诱导IL-4。这些结果证明了γ-溶血素的一种新功能，即以IgE非依赖性方式诱导嗜碱性粒细胞中的IL-4。
Basophils are known to produce a large amount of IL-4 in response to stimuli and play a role in the initiation and propagation of type 2 inflammations.S. aureussecretes a series of pore-forming toxins: α-hemolysin, γ-hemolysins, and leukocidins. In this study, we examined the effects of α-hemolysin, γ-hemolysins (HlgAB and HlgCB), and leukocidins (LukAB, LukED, and Panton-Valentine leukocidin) on the function of basophils. All pore-forming toxins except for Panton-Valentine leukocidin bound to murine bone marrow-derived basophils (BMBs). HlgAB and LukED but not other toxins evoked the leakage of lactate dehydrogenase from BMBs at the concentration of 30 μg/ml γ-hemolysins, HlgAB and HlgCB, induced the secretion of IL-4 in BMBs at concentrations above 3.3 μg/ml. LukAB did not induce, and Hla and LukED induced only a small amount of IL-4. HlgBΔstem, the 5 amino acids deletion mutant of HlgB in the stem region, diminished IL-4 secretion by HlgAB and HlgCB in BMBs. These results suggest that the cell damage and the induction of IL-4 in basophils by HlgAB require pore formation. The induction of IL-4 by γ-hemolysins was also observed in fleshly isolated murine basophils. These results demonstrate a novel function of γ-hemolysins, the induction of IL-4 in basophils, in an IgE-independent manner.