Table_1_Toxoplasma gondii Infection Inhibits Histone Crotonylation to Regulate Immune Response of Porcine Alveolar Macrophages.xlsx

Toxoplasma gondii (T. gondii) is an obligate intracellular parasite that can infect almost all warm-blooded animals, causing serious public health problems. Lysine crotonylation (Kcr) is a newly discovered posttranslational modification (PTM), which is first identified on histones and has been proved relevant to procreation regulation, transcription activation, and cell signaling pathway. However, the biological functions of histone crotonylation have not yet been reported in macrophages infected with T. gondii. As a result, a total of 1,286 Kcr sites distributed in 414 proteins were identified and quantified, demonstrating the existence of crotonylation in porcine alveolar macrophages. According to our results, identified histones were overall downregulated. HDAC2, a histone decrotonylase, was found to be significantly increased, which might be the executor of histone Kcr after parasite infection. In addition, T. gondii infection inhibited the crotonylation of H2B on K12, contributing on the suppression of epigenetic regulation and NF-κB activation. Nevertheless, the reduction of histone crotonylation induced by parasite infection could promote macrophage proliferation via activating PI3K/Akt signaling pathway. The present findings point to a comprehensive understanding of the biological functions of histone crotonylation in porcine alveolar macrophages, thereby providing a certain research basis for the mechanism research on the immune response of host cells against T. gondii infection.

刚地弓形虫（Toxoplasma gondii, T. gondii）是一种专性细胞内寄生虫，可感染几乎所有温血动物，引发严重的公共卫生问题。赖氨酸巴豆酰化（Lysine crotonylation, Kcr）是一种新发现的翻译后修饰（posttranslational modification, PTM），最初在组蛋白上被鉴定，现已被证实与生殖调控、转录激活及细胞信号通路密切相关。然而，弓形虫感染巨噬细胞后，组蛋白巴豆酰化的生物学功能尚未见报道。本研究共鉴定并定量了分布于414种蛋白质中的1286个Kcr位点，证实猪肺泡巨噬细胞中存在组蛋白巴豆酰化修饰。研究结果显示，所鉴定的组蛋白整体表达水平下调。组蛋白去巴豆酰化酶HDAC2的表达显著升高，其可能是寄生虫感染后介导组蛋白Kcr调控的关键效应分子。此外，弓形虫感染可抑制组蛋白H2B的K12位点巴豆酰化，进而参与表观遗传调控与核因子κB（NF-κB）激活的抑制过程。不过，寄生虫感染诱导的组蛋白巴豆酰化水平降低，可通过激活PI3K/Akt信号通路促进巨噬细胞增殖。本研究结果全面阐明了组蛋白巴豆酰化在猪肺泡巨噬细胞中的生物学功能，为宿主细胞抗刚地弓形虫感染的免疫应答机制研究提供了一定的理论依据。