Modulation of human bronchial epithelial cells by pneumococcal choline binding protein A.
Choline binding protein A (CbpA) is an important adhesin and a determinant of virulence for Streptococcus pneumoniae. Binding to epithelial cells of host mucosal surfaces by pneumococcal CbpA is essential for pneumococcus to initiate colonization and to trigger subsequent invasive pneumococcal infections. In this study, we examined the immunopathologic mechanisms for the activation of human bronchial epithelial cells by CbpA in pneumococcal infections. Adhesion molecules, cytokines, and chemokines were assessed by flow cytometry, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. Intracellular signaling molecules were investigated by enzyme-linked immunosorbent assay or transcription factor assay. CbpA could upregulate cell surface expression of adhesion molecule intercellular adhesion molecule-1 on human bronchial epithelial cells. CbpA could also induce the release of inflammatory cytokine interleukin-6, and chemokines CCL2, CXCL1, and CXCL8 from human bronchial epithelia cells. CbpA-mediated induction of these mediators was differentially regulated by extracellular signal-regulated kinase, c-Jun N-terminal protein kinase, p38-mitogen-activated protein kinase, and nuclear factor-κB pathways. CbpA was also found to participate in the induction of IL-6, CCL2, CXCL1, and CXCL8 in the airways of mice upon intranasal challenge with S. pneumoniae. Our study therefore suggests that pneumococcal CbpA plays an immunopathophysiologic role by activating human bronchial epithelial cells in pneumococcal infections.
Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China. doccjhx@163.com
Ju
J
Cao
Yi
Y
Gong
Bei
B
Cai
Weihua
W
Feng
Yongkang
Y
Wu
Lixin
L
Li
Yuangao
Y
Zou
Binwu
B
Ying
Lanlan
L
Wang
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism
D057134:Antibodies, Neutralizing; D001426:Bacterial Proteins; D018925:Chemokines; D016207:Cytokines; D016328:NF-kappa B; C110344:SpsA protein, Streptococcus pneumoniae; D018799:Intercellular Adhesion Molecule-1; D020928:Mitogen-Activated Protein Kinases