Department of Neonatology, Heidelberg University Children's Hospital, 69120 Heidelberg, Germany.
Klinik für Kinderheilkunde und Jugendmedizin, 87700 Memmingen, Germany.
Cell Immunol. 2022 Jun;376:104535. doi: 10.1016/j.cellimm.2022.104535. Epub 2022 May 4.
Neutrophils primarily act as first responders in acute infection and directly maintain inflammatory responses. However, a growing body of evidence suggests that neutrophils also bear the potential to mediate chronic inflammation by exhibiting memory-like features. We now asked whether bone marrow-derived murine neutrophils can be primed by lipoteichoic acid (LTA) from gram-positive S. aureus. We found that low-dose (1 ng/mL) LTA-priming promoted increased production of pro-inflammatory mediators (TNF-α, IL-6, ROS), whereas high-dose (10 µg/mL) priming resulted in opposing reactions marked by increased IL-10 and suppressed pro-inflammatory mediators upon a second stimulus. A similar pattern of pro-inflammatory activation (trained sensitivity) and anti-inflammatory properties (tolerance) was recapitulated in cellular functional in vitro assays (transmigration and phagocytosis). Priming by LTA correlated with TLR2/MyD88-mediated regulation of NFκB-p65 through intermediate PI3Ks/MAPK. Collectively, our data suggest a previously unknown capacity of neutrophils to be differentially primed by varying doses of LTA, endorsing memory-like features in neutrophils.
中性粒细胞主要作为急性感染的一线反应细胞，并直接维持炎症反应。然而，越来越多的证据表明，中性粒细胞也有可能通过表现出类似记忆的特征来介导慢性炎症。我们现在想知道，革兰氏阳性金黄色葡萄球菌的脂磷壁酸（LTA）是否可以对骨髓来源的鼠中性粒细胞进行预刺激。我们发现，低剂量（1ng/ml）LTA 预刺激可促进促炎介质（TNF-α、IL-6、ROS）的产生增加，而高剂量（10μg/ml）预刺激则导致相反的反应，以第二次刺激时增加的 IL-10 和抑制的促炎介质为特征。在细胞功能体外测定（迁移和吞噬）中，也重现了类似的促炎激活（训练敏感性）和抗炎特性（耐受性）的模式。LTA 的预刺激与 TLR2/MyD88 介导的 NFκB-p65 通过中间 PI3K/MAPK 的调节有关。总的来说，我们的数据表明，中性粒细胞可以被不同剂量的 LTA 以不同的方式预刺激，从而赋予中性粒细胞类似记忆的特征，这是以前未知的。
