title: TBX21 participates in innate immune response by regulating Toll-like receptor 2 expression in Streptococcus pneumoniae infections.
abstract: Nasopharyngeal carriage of Streptococcus pneumoniae (pneumococcus) plays an important role in the development of invasive diseases, and is also critically involved in setting up respiratory bacterial and viral infections. We previously reported that pneumococcus, one of the commonly carried bacteria in the nasopharynx, regulates non-typeable Haemophilus influenzae-induced inflammation by upregulating the expression of Toll-like receptor 2 (TLR2). However, the underlying molecular mechanisms by which TLR2 expression is regulated during pneumococcal infections have not yet been well characterized. TBX21 is an important transcription factor of adaptive immunity, but there is an increasing body of evidence pointing to a role in regulating innate immunity. The expression of TBX21 was reported in epithelial cells, but the expression and role of TBX21 in respiratory epithelium, especially for regulating TLR2, has not yet been studied. In this study, we found that pneumococcus upregulates TBX21 expression in the respiratory epithelium. The effect of pneumococcus on TBX21 expression was dependent on its cytoplasmic toxin, pneumolysin. In addition, epithelial TBX21 expression was not regulated by the gram-negative bacterium non-typeable Haemophilus influenzae, peptidoglycan or endotoxin. Deficiency of TBX21 in mice or knocking down TBX21 in epithelial cells suppressed pneumococcus-induced TLR2 expression, but not that of TLR4 or TLR9. These results indicate that the adaptive immune regulator TBX21 participates in regulating innate immune responses, through regulation of TLR2 expression during pneumococcal infections.
authors.affiliation: Department of Pharmacology, Yeungnam University College of Medicine, Daegu, Korea.
authors.forename: C H
authors.initials: CH
authors.lastname: Woo
authors.forename: S G
authors.initials: SG
authors.lastname: Shin
authors.forename: S H
authors.initials: SH
authors.lastname: Koh
authors.forename: J H
authors.initials: JH
authors.lastname: Lim
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D004432:Ear, Middle / Q000276:immunology; D004731:Endotoxins / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology; D055785:Gene Knockdown Techniques; D006193:Haemophilus influenzae / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010033:Otitis Media / Q000276:immunology / Q000382:microbiology; D010457:Peptidoglycan / Q000276:immunology; D011008:Pneumococcal Infections / Q000276:immunology*; D011018:Pneumonia, Pneumococcal / Q000276:immunology; D011650:Pulmonary Alveoli / Q000276:immunology; D034741:RNA, Small Interfering / Q000235:genetics; D020545:Respiratory Mucosa / Q000276:immunology; D013301:Streptolysins / Q000276:immunology; D020825:T-Box Domain Proteins / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000032:analysis; D051217:Toll-Like Receptor 9 / Q000032:analysis; D015854:Up-Regulation; D000098815:T-bet Transcription Factor
chemical_list: D001426:Bacterial Proteins; D004731:Endotoxins; D010457:Peptidoglycan; D034741:RNA, Small Interfering; D013301:Streptolysins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; C495370:Tlr9 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; C032290:plY protein, Streptococcus pneumoniae
keywords: TBX21; Toll-like receptor 2; pneumococcus; pneumolysin