title: Purified Streptococcus pneumoniae Endopeptidase O (PepO) Enhances Particle Uptake by Macrophages in a Toll-Like Receptor 2- and miR-155-Dependent Manner.
abstract: Insights into the host-microbial virulence factor interaction, especially the immune signaling mechanisms, could provide novel prevention and treatment options for pneumococcal diseases.Streptococcus pneumoniaeendopeptidase O (PepO) is a newly discovered and ubiquitously expressed pneumococcal virulence protein. A PepO-mutant strain showed impaired adherence to and invasion of host cells compared with the isogenic wild-type strain. It is still unknown whether PepO is involved in the host defense response to pneumococcal infection. Here, we demonstrated that PepO could enhance phagocytosis ofStreptococcus pneumoniaeandStaphylococcus aureusby peritoneal exudate macrophages (PEMs). Further studies showed that PepO stimulation upregulated the expression of microRNA-155 (miR-155) in PEMs in a time- and dose-dependent manner. PepO-induced enhanced phagocytosis was decreased in cells transfected with an inhibitor of miR-155, while it was increased in cells transfected with a mimic of miR-155. We also revealed that PepO-induced upregulation of miR-155 in PEMs was mediated by Toll-like receptor 2 (TLR2)-NF-κB signaling and that the increased expression of miR-155 downregulated expression of SHIP1. Taken together, these results indicate that PepO induces upregulation of miR-155 in PEMs, contributing to enhanced phagocytosis and host defense response to pneumococci andStaphylococcus aureus.
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing, People's Republic of China.|Department of Laboratory Medicine, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yao
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing, People's Republic of China.|Department of Laboratory Medicine, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, Guangdong Provincial Hospital of T.C.M. (Traditional Chinese Medicine), Guangzhou, People's Republic of China.
authors.forename: Kai
authors.initials: K
authors.lastname: Lan
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Dagen
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Cui
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing, People's Republic of China apoe@163.com.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D010587:Phagocytosis; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases / Q000235:genetics; D011008:Pneumococcal Infections / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D034622:RNA Interference; D015398:Signal Transduction; D013211:Staphylococcus aureus / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D051195:Toll-Like Receptor 2; C000606433:Inpp5d protein, mouse; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D008666:Metalloendopeptidases; C080385:oligopeptidase PepO
keywords: PepO; TLR2; macrophages; miR-155; phagocytosis