Department of Infectious Diseases and Microbiology, University of Lübeck, Lübeck, Germany.
Front Immunol. 2021 Oct 18;12:747049. doi: 10.3389/fimmu.2021.747049. eCollection 2021.
Although macrophages are considered for host cells for the multiplication of , recent studies indicate the important role of neutrophil granulocytes as host cells for these intracellular parasites. Neutrophils have been shown to be massively and rapidly recruited to the site of infection where they represent the first cells to encounter the parasites. Exposure to ATP and UTP have been shown to enhance anti- activity of macrophages and intralesional injection of UTP led to strongly reduced parasite load . Since the anti-leishmanial effect of extracellular UTP correlated with enhanced neutrophil recruitment and enhanced ROS production at the site of infection we hypothesized that exposure to extracellular nucleotides can directly enhance the killing of by neutrophils. Since purinergic signaling is an essential mechanism of neutrophil activation the aim of the present study was to assess whether purinergic exposure results in the activation of anti-leishmanial neutrophil functions and, therefore, represent an essential component of enhanced anti-leishmanial defense in leishmaniasis. We could show that exposure to ATP and UTP led to activation and enhanced CD11b expression of primary human neutrophils . -induced ROS production was strongly enhanced by extracellular ATP and UTP. Importantly, exposure to ATP and UTP resulted in enhanced killing of by neutrophils. In addition, ATP strongly enhanced the secretion of IL-8 and IL-1β by -exposed neutrophils. Our results suggest that signaling the P2 receptor and phosphorylation of Erk1/2, Akt and p38 are involved in the purinergic enhancement of anti-leishmanial functions of neutrophils.
虽然巨噬细胞被认为是寄生虫繁殖的宿主细胞，但最近的研究表明中性粒细胞在这些细胞内寄生虫的宿主细胞中起着重要作用。已经表明中性粒细胞大量且迅速募集到感染部位，它们是首先遇到寄生虫的细胞。已经表明暴露于 ATP 和 UTP 可增强巨噬细胞的抗活性，并且局部注射 UTP 可导致寄生虫载量大大降低。由于细胞外 UTP 的抗利什曼原虫作用与感染部位中性粒细胞募集的增强和 ROS 产生的增强相关，我们假设暴露于细胞外核苷酸可以直接增强中性粒细胞对的杀伤作用。由于嘌呤能信号是中性粒细胞激活的重要机制，本研究的目的是评估嘌呤能暴露是否导致抗利什曼原虫中性粒细胞功能的激活，因此是增强利什曼病中抗利什曼防御的重要组成部分。我们可以证明，暴露于 ATP 和 UTP 导致原代人中性粒细胞的激活和 CD11b 表达增强。由诱导的 ROS 产生被细胞外 ATP 和 UTP 强烈增强。重要的是，暴露于 ATP 和 UTP 导致中性粒细胞对的杀伤增强。此外，ATP 强烈增强了暴露于的中性粒细胞分泌的 IL-8 和 IL-1β。我们的结果表明，嘌呤能信号传导 P2 受体和 Erk1/2、Akt 和 p38 的磷酸化参与了中性粒细胞抗利什曼原虫功能的嘌呤能增强。
