Atopic individuals show enhanced type 2 immune cell responses and a susceptibility to infections with certain bacteria and viruses. Although patients with allergic diseases harbor normal counts of circulating neutrophils, these cells exert deficient effector functions. However, the underlying mechanism of this dysregulation of neutrophils remains ill defined. Here, we find that development, aging, and elimination of neutrophils are accelerated in mice with a predisposition to type 2 immunity, which, in turn, causes susceptibility to infection with several bacteria. Neutrophil-mediated immunity to bacterial infection was greatly decreased in mice with a genetic or induced bias to type 2 immunity. Abrogation of interleukin-4 (IL-4) receptor signaling in these animals fully restored their antibacterial defense, which largely depended on Ly6G+ neutrophils. IL-4 signals accelerated the maturation of neutrophils in the bone marrow and caused their rapid release to the circulation and periphery. IL-4-stimulated neutrophils aged more rapidly in the periphery, as evidenced by their phenotypic and functional changes, including their decreased phagocytosis of bacterial particles. Moreover, neutrophils from type 2 immune predisposed mice were eliminated at a higher rate by apoptosis and phagocytosis by macrophages and dendritic cells. Collectively, IL-4 signaling-mediated neutrophil aging constitutes an important adaptive deficiency in type 2 inflammation, contributing to recurrent bacterial infections.

中文翻译：

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2 型免疫易感性导致中性粒细胞加速老化，从而导致对细菌感染的易感性。

特应性个体表现出增强的 2 型免疫细胞反应和对某些细菌和病毒感染的易感性。尽管过敏性疾病患者的循环中性粒细胞计数正常，但这些细胞发挥的效应功能不足。然而，这种中性粒细胞失调的潜在机制仍不清楚。在这里，我们发现在具有 2 型免疫倾向的小鼠中，嗜中性粒细胞的发育、衰老和消除会加速，这反过来又会导致对几种细菌的感染易感性。在具有遗传或诱导偏向 2 型免疫的小鼠中，中性粒细胞介导的对细菌感染的免疫力大大降低。这些动物中白细胞介素 4 (IL-4) 受体信号的消除完全恢复了它们的抗菌防御，这在很大程度上取决于 Ly6G+ 中性粒细胞。IL-4 信号加速了骨髓中中性粒细胞的成熟，并导致它们迅速释放到循环和外周。IL-4 刺激的中性粒细胞在外周老化得更快，这可以通过它们的表型和功能变化来证明，包括它们对细菌颗粒的吞噬作用降低。此外，来自 2 型免疫易感小鼠的中性粒细胞通过凋亡和巨噬细胞和树突状细胞的吞噬作用以更高的速率被消除。总的来说，IL-4 信号介导的中性粒细胞衰老构成 2 型炎症的重要适应性缺陷，导致细菌感染复发。IL-4 刺激的中性粒细胞在外周老化得更快，这可以通过它们的表型和功能变化来证明，包括它们对细菌颗粒的吞噬作用降低。此外，来自 2 型免疫易感小鼠的中性粒细胞通过凋亡和巨噬细胞和树突状细胞的吞噬作用以更高的速率被消除。总的来说，IL-4 信号介导的中性粒细胞衰老构成 2 型炎症的重要适应性缺陷，导致细菌感染复发。IL-4 刺激的中性粒细胞在外周老化得更快，这可以通过它们的表型和功能变化来证明，包括它们对细菌颗粒的吞噬作用降低。此外，来自 2 型免疫易感小鼠的中性粒细胞通过凋亡和巨噬细胞和树突状细胞的吞噬作用以更高的速率被消除。总的来说，IL-4 信号介导的中性粒细胞衰老构成 2 型炎症的重要适应性缺陷，导致细菌感染复发。