RRC ID 50796
著者 Matsushima H, Kumagai Y, Vandenbon A, Kataoka H, Kadena M, Fukamachi H, Arimoto T, Morisaki H, Fujiwara N, Okahashi N, Kuwata H.
タイトル Microarray analysis of macrophage response to infection with Streptococcus oralis reveals the immunosuppressive effect of hydrogen peroxide.
ジャーナル Biochem Biophys Res Commun
Abstract Oral streptococci including mitis group streptococci are commensal residents and are also the first to colonize the oral cavity. However, various species of these oral streptococci have the potential to invade the host and occasionally lead to severe infectious disease such as cardiovascular diseases. Oral streptococci have close interactions with the host immune system including macrophages at the oral mucosal surface. One notable common trait of oral streptococcus including Streptococcus oralis (S. oralis) is the production of hydrogen peroxide (H2O2). Using a comprehensive microarray approach, we sought to understand the innate immune response profiling affected by H2O2 production from oral streptococci. We compared the gene expression patterns of macrophages infected with S. oralis wild type (WT) and streptococcal pyruvate oxidase knockout (SpxB-KO), a strain that does not produce H2O2. We found that H2O2 from S. oralis suppressed proinflammatory gene expression such as TNF-α, that is induced in response to infection, and activated the cellular stress genes such as Egr-1 in response to oxidative stress. A comparative gene ontology analysis of S. oralis WT and SpxB-KO strains revealed that during infection, down regulated genes were closely related to the processes involved in the host defense reaction and up regulated genes were related with the cellular stress responses. Using qPCR analysis, we also confirmed the same pattern of expression changes such as TNF-α, IL-6 and Egr-1. Furthermore, supernatant from SpxB-KO could not suppress the expression of TNF-α in macrophages stimulated with LPS. These findings suggested that H2O2 production from S. oralis leads to the suppression of inflammatory responses and NF-κB signaling pathways in macrophages as well as the induction of the oxidative stress response. We concluded that streptococcal H2O2 production has the beneficial effects of modulating the innate immune response, thereby stabilizing streptococcal colonization at the mucosal surface and even in the bloodstream leading to cardiovascular disease after invasion, in addition to the commensal role to compete other bacterial species as initial colonizer at oral cavity.
巻・号 485(2)
ページ 461-467
公開日 2017-4-1
DOI 10.1016/j.bbrc.2017.02.048
PII S0006-291X(17)30316-9
PMID 28202416
MeSH 3T3 Cells Animals Bacterial Proteins / genetics Bacterial Proteins / metabolism Blotting, Western Cell Line Cluster Analysis Early Growth Response Protein 1 / genetics Early Growth Response Protein 1 / metabolism Gene Expression Profiling / methods* Gene Ontology Host-Pathogen Interactions Hydrogen Peroxide / metabolism* Interleukin-6 / genetics Interleukin-6 / metabolism Lipopolysaccharides / pharmacology Macrophages / drug effects Macrophages / metabolism* Macrophages / microbiology Mice Mice, Inbred BALB C Mutation Oligonucleotide Array Sequence Analysis / methods* Pyruvate Oxidase / genetics Pyruvate Oxidase / metabolism Reverse Transcriptase Polymerase Chain Reaction Streptococcus oralis / genetics Streptococcus oralis / metabolism* Streptococcus oralis / physiology Tumor Necrosis Factor-alpha / genetics Tumor Necrosis Factor-alpha / metabolism
IF 2.985
引用数 2
リソース情報
一般微生物 JCM 12997