Toxoplasma gondii Infection Inhibits Histone Crotonylation to Regulate Immune Response of Porcine Alveolar Macrophages

• Published in: Frontiers in immunology Vol. 12; p. 696061
• Main Authors: Yang, Jing, He, Zhengming, Chen, Chengjie, Li, Senyang, Qian, Jiahui, Zhao, Junlong, Fang, Rui
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 08.07.2021
• Subjects: Animals; Cell Line; Cell Proliferation; Crotonates - metabolism; Epigenesis, Genetic; histone crotonylation; Histones - metabolism; Host-Parasite Interactions; immune response; Immunology; Macrophage Activation; Macrophages, Alveolar - immunology; Macrophages, Alveolar - metabolism; Macrophages, Alveolar - parasitology; NF-kappa B - metabolism; porcine alveolar macrophage; posttranslation modification; Protein Processing, Post-Translational; Signal Transduction; Sus scrofa; Toxoplasma - immunology; Toxoplasma - parasitology; Toxoplasma gondii; Toxoplasmosis - immunology; Toxoplasmosis - metabolism; Toxoplasmosis - parasitology; porcine alveolar macrophage; Toxoplasma gondii; histone crotonylation; posttranslation modification; immune response
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.696061

( ) 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 . 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, infection inhibited the crotonylation of H2B on K12, contributing on the suppression of epigenetic regulation and NF- B activation. Nevertheless, the reduction of histone crotonylation induced by parasite infection could promote macrophage proliferation 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 infection.