RRC ID 56143
Author Nagai K, Domon H, Maekawa T, Oda M, Hiyoshi T, Tamura H, Yonezawa D, Arai Y, Yokoji M, Tabeta K, Habuka R, Saitoh A, Yamaguchi M, Kawabata S, Terao Y.
Title Pneumococcal DNA-binding proteins released through autolysis induce the production of proinflammatory cytokines via toll-like receptor 4.
Journal Cell Immunol
Abstract Streptococcus pneumoniae is a leading cause of bacterial pneumonia. Our previous study suggested that S. pneumoniae autolysis-dependently releases intracellular pneumolysin, which subsequently leads to lung injury. In this study, we hypothesized that pneumococcal autolysis induces the leakage of additional intracellular molecules that could increase the pathogenicity of S. pneumoniae. Liquid chromatography tandem-mass spectrometry analysis identified that chaperone protein DnaK, elongation factor Tu (EF-Tu), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were released with pneumococcal DNA by autolysis. We demonstrated that recombinant (r) DnaK, rEF-Tu, and rGAPDH induced significantly higher levels of interleukin-6 and tumor necrosis factor production in peritoneal macrophages and THP-1-derived macrophage-like cells via toll-like receptor 4. Furthermore, the DNA-binding activity of these proteins was confirmed by surface plasmon resonance assay. We demonstrated that pneumococcal DnaK, EF-Tu, and GAPDH induced the production of proinflammatory cytokines in macrophages, and might cause host tissue damage and affect the development of pneumococcal diseases.
Volume 325
Pages 14-22
Published 2018-3
DOI 10.1016/j.cellimm.2018.01.006
PII S0008-8749(18)30006-6
PMID 29366563
MeSH Animals Autolysis / metabolism* Bacterial Proteins Chromatography, Liquid / methods Cytokines / metabolism DNA-Binding Proteins / metabolism* DNA-Binding Proteins / physiology Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism Humans Macrophages / metabolism Macrophages, Peritoneal / metabolism Male Mice Mice, Inbred BALB C Molecular Chaperones / metabolism Peptide Elongation Factor Tu / metabolism Pneumococcal Infections / genetics Streptococcus pneumoniae / genetics Streptococcus pneumoniae / metabolism* THP-1 Cells Tandem Mass Spectrometry / methods Toll-Like Receptor 4 / immunology Toll-Like Receptor 4 / metabolism
IF 3.291
Times Cited 6
Human and Animal Cells THP-1(RCB1189)