title: Immune response of macrophages induced by Porphyromonas gingivalis requires HmuY protein.
abstract: The main etiologic agent and a key pathogen responsible for initiation and progression of chronic periodontitis is Porphyromonas gingivalis. We examined the role of P. gingivalis, with particular interest to HmuY protein, in expression of genes involved in Toll-like receptor (TLR)-induced signaling pathways using cell-based infection model. U937 and THP-1 cells differentiated toward macrophages by PMA treatment responded to P. gingivalis-caused infection in slightly different gene expression pattern, mainly by higher expression of genes encoding NF-κB, TLR7, TLR2, TLR8, pro-inflammatory cytokines (IL-1β, IL-6, TNFα), anti-inflammatory cytokine (IL-10), and chemokines (CCL3L1, CCL4, CXCL10, CXCL11, PTX3). P. gingivalis lacking functional hmuY gene stimulates immune response of macrophages, albeit in a different manner as compared with the wild-type strain, mainly by lower expression of genes encoding NF-κB, IL-1β, IL-10, CD80, PTX3, and CCL31L. The purified HmuY protein alone induced expression of genes encoding IL-6, IL-10, TNFα, CCL3L1, and CCL4. We conclude that macrophages respond to P. gingivalis infection mostly by TLR7-induced pathway(s). Moreover, P. gingivalis HmuY is one of important virulence factors, which allows P. gingivalis for in vivo growth in the heme-limited host environment, resulting in efficient immune response of macrophages.
authors.affiliation: Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Gmiterek
authors.affiliation: Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kłopot
authors.affiliation: Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland.
authors.forename: Halina
authors.initials: H
authors.lastname: Wójtowicz
authors.affiliation: Department of Health, Feira de Santana State University, Bahia, Brazil.
authors.forename: Soraya C
authors.initials: SC
authors.lastname: Trindade
authors.affiliation: Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Olczak
authors.affiliation: Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland. Electronic address: teresa.olczak@uwr.edu.pl.
authors.forename: Teresa
authors.initials: T
authors.lastname: Olczak
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016866:Bacteroidaceae Infections / Q000276:immunology*; D002454:Cell Differentiation; D048708:Cell Growth Processes; D055113:Chronic Periodontitis / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D000069452:Pathogen-Associated Molecular Pattern Molecules / Q000276:immunology; D016966:Porphyromonas gingivalis / Q000276:immunology* / Q000472:pathogenicity; D015398:Signal Transduction; D000074084:THP-1 Cells; D051199:Toll-Like Receptor 7 / Q000378:metabolism; D059467:Transcriptome; D020298:U937 Cells; D014774:Virulence
chemical_list: D001425:Bacterial Outer Membrane Proteins; D016207:Cytokines; D000069452:Pathogen-Associated Molecular Pattern Molecules; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7
keywords: Cytokine; HmuY; Macrophage; Periodontitis; Porphyromonas gingivalis; Toll-like receptor