Epithelial cells maintain memory of prior infection withStreptococcus pneumoniaethrough di-methylation of histone H3

Autor: Melanie Hamon, Christine Chevalier, Claudia Chica, Justine Matheau, Michael Connor, Adrien Pain
Přispěvatelé: Chromatine et Infection - Chromatin and Infection, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, École Doctorale Bio Sorbonne Paris Cité [Paris] (ED562 - BioSPC), Université Sorbonne Paris Cité (USPC)-Université Paris Cité (UPCité), Work in the Chromatin and Infection Unit (headed by Melanie Hamon) is supported by the Institut Pasteur, the Agence Nationale de la Recherche (ANR 17 CE12 0007 01 EPIBACTIN),the Fondation pour la Recherche Médicale (FRM608 EQU202003010152), the Fondation iXCore-iXLife, the Don Prix CANETTI 2020, the EMBO Young Investigator Program.M.A.H. is a member of the Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' Agence Nationale de la Recherche (ANR-10-LABX- 62-IBEID). M.G.C. is supported by a Springboard to Independence grant (AirwayStasis) from the French Government’s Investissement d’Avenir program, the Laboratoire d’Excellence ‘‘Integrative Biology of Emerging Infectious Diseases' (ANR-10-LABX-62-605IBEID) and Pasteur-Weizmann research fund. Bioinformatics and Biostatistics Hub is supported by Institut Pasteur., ANR-17-CE12-0007,EpiBactIn,Modifications epigenomiques induites par l'interaction hote-bacteries(2017), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
Rok vydání: 2023
Předmět:
DOI: 10.1101/2023.05.19.541441
Popis: Epithelial cells are the first point of contact for bacteria entering the respiratory tract. Streptococcus pneumoniae is an obligate human pathobiont of the nasal mucosa, carried asymptomatically but also the cause of severe pneumonia. The role of the epithelium in maintaining homeostatic interactions or mounting an inflammatory response to invasive S. pneumoniae is currently poorly understood. However, studies have shown that chromatin modifications, at the histone level, induced by bacterial pathogens interfere with the host transcriptional program and promote infection. In this study, we demonstrate that S. pneumoniae actively induces di-methylation of lysine 4 on histone H3 (H3K4me2), which persists for at least 9 days upon clearance of bacteria with antibiotics. We show that infection establishes a unique epigenetic program affecting the transcriptional response of epithelial cells, rendering them more permissive upon secondary infection. Our results establish H3K4me2 as a unique modification induced by infection, distinct from H3K4me3, which localizes to enhancer regions genome-wide. Therefore, this study reveals evidence that bacterial infection leaves a memory in epithelial cells after bacterial clearance, in an epigenomic mark, thereby altering cellular responses for subsequent infection.
Databáze: OpenAIRE