Pneumococcal DNA-binding proteins released through autolysis induce the production of proinflammatory cytokines via toll-like receptor 4.

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.

• Authors: Kosuke Nagai, Hisanori Domon, Tomoki Maekawa, Masataka Oda, Takumi Hiyoshi, Hikaru Tamura, Daisuke Yonezawa, Yoshiaki Arai, Mai Yokoji, Koichi Tabeta, Rie Habuka, Akihiko Saitoh, Masaya Yamaguchi, Shigetada Kawabata, Yutaka Terao
• Journal: Cellular immunology (Cell Immunol) Vol. 325 Pg. 14-22 (03 2018) ISSN: 1090-2163 [Electronic] Netherlands
• PMID: 29366563 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Bacterial Proteins
• Cytokines
• DNA-Binding Proteins
• Molecular Chaperones
• Toll-Like Receptor 4
• Glyceraldehyde-3-Phosphate Dehydrogenases
• Peptide Elongation Factor Tu

Topics

• Animals
• Autolysis (metabolism)
• Bacterial Proteins
• Chromatography, Liquid (methods)
• Cytokines (metabolism)
• DNA-Binding Proteins (metabolism, 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, metabolism)
• THP-1 Cells
• Tandem Mass Spectrometry (methods)
• Toll-Like Receptor 4 (immunology, metabolism)