鲤鱼的红细胞是免疫哨兵,可以感知病原体分子模式、吞噬颗粒并分泌促炎细胞因子来抵抗细菌感染。
Erythrocytes of the common carp are immune sentinels that sense pathogen molecular patterns, engulf particles and secrete pro-inflammatory cytokines against bacterial infection.
发表日期:2024
作者:
Jovana Majstorović, Jiří Kyslík, Katarzyna Klak, Magdalena Maciuszek, Justin T H Chan, Tomáš Korytář, Astrid S Holzer
来源:
Parasites & Vectors
摘要:
红细胞 (RBC),也称为红细胞,其在免疫系统中的作用被低估。在哺乳动物中,红细胞经历成熟过程,导致细胞核丢失,导致转录和蛋白质合成能力有限。然而,非哺乳动物红细胞的有核性质正在挑战对红细胞的传统理解。值得注意的是,研究表明,在硬骨鱼中,红细胞不仅容易受到病原体攻击,而且还表达免疫受体和效应分子。然而,考虑到红细胞的丰富性及其与每个生理系统的相互作用,我们假设它们在监视中充当哨兵、快速反应者和信使。我们对暴露于嗜水气单胞菌的鲤鱼红细胞进行了一系列体外实验。正如使用不同浓度细菌的体内实验室感染一样。qPCR 显示红细胞表达几种炎症细胞因子的基因。使用鲤鱼特异性抗体,我们证实红细胞分泌肿瘤坏死因子α(TNFα)和干扰素γ(IFNγ)。与这些间接免疫机制相反,我们观察到红细胞产生活性氧,并且通过透射电子和共聚焦显微镜,红细胞可以吞噬颗粒。最后,红细胞表达并上调几种假定的 Toll 样受体,包括 tlr4 和 tlr9,以响应体内嗜水气单胞菌感染。总体而言,红细胞的模式识别受体库、效应分子的分泌及其快速反应使它们免疫哨兵能够快速检测并发出外来病原体存在的信号。通过研究细菌和红细胞之间的相互作用,我们提供了关于后者如何促进硬骨鱼整体先天性和适应性免疫反应的新见解。版权所有 © 2024 Majstorović、Kyslík、Klak、Maciuszek、Chan、Korytář 和 Holzer。
Red blood cells (RBCs), also known as erythrocytes, are underestimated in their role in the immune system. In mammals, erythrocytes undergo maturation that involves the loss of nuclei, resulting in limited transcription and protein synthesis capabilities. However, the nucleated nature of non-mammalian RBCs is challenging this conventional understanding of RBCs. Notably, in bony fishes, research indicates that RBCs are not only susceptible to pathogen attacks but express immune receptors and effector molecules. However, given the abundance of RBCs and their interaction with every physiological system, we postulate that they act in surveillance as sentinels, rapid responders, and messengers.We performed a series of in vitro experiments with Cyprinus carpio RBCs exposed to Aeromonas hydrophila, as well as in vivo laboratory infections using different concentrations of bacteria.qPCR revealed that RBCs express genes of several inflammatory cytokines. Using cyprinid-specific antibodies, we confirmed that RBCs secreted tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ). In contrast to these indirect immune mechanisms, we observed that RBCs produce reactive oxygen species and, through transmission electron and confocal microscopy, that RBCs can engulf particles. Finally, RBCs expressed and upregulated several putative toll-like receptors, including tlr4 and tlr9, in response to A. hydrophila infection in vivo.Overall, the RBC repertoire of pattern recognition receptors, their secretion of effector molecules, and their swift response make them immune sentinels capable of rapidly detecting and signaling the presence of foreign pathogens. By studying the interaction between a bacterium and erythrocytes, we provide novel insights into how the latter may contribute to overall innate and adaptive immune responses of teleost fishes.Copyright © 2024 Majstorović, Kyslík, Klak, Maciuszek, Chan, Korytář and Holzer.