title: Streptococcus pneumoniae Endopeptidase O (PepO) Elicits a Strong Innate Immune Response in Mice via TLR2 and TLR4 Signaling Pathways.
abstract: Interaction between virulence factors of Streptococcus pneumoniae and innate immune receptors elicits host responses through specific signaling pathways during infection. Insights into the signaling events may provide a better knowledge of the starting events for host-pathogen interaction. Here we demonstrated a significant induction of innate immune response elicited by recombinant S. pneumoniae endopeptidase O (rPepO), a newer pneumococcal virulence protein, both in vivo and in vitro. Intratracheal instillation of rPepO protein resulted in significant increase of cytokines production and neutrophils infiltration in mouse lungs. TLR2 or TLR4 deficient mice subjected to rPepO treatment showed decreased cytokines production, reduced neutrophils infiltration and intensified tissue injury as compared with WT mice. Upon stimulation, cytokines TNF-α, IL-6, CXCL1, and CXCL10 were produced by peritoneal exudate macrophages (PEMs) in a TLR2 and TLR4 dependent manner. rPepO-induced cytokines production was markedly decreased in TLR2 or TLR4 deficient PEMs. Further study revealed that cytokines induction relied on the rapid phosphorylation of p38, Akt and p65, not the activation of ERK or JNK. While in TLR2 or TLR4 deficient PEMs the activation of p65 was undetectable. Taken together, these results indicate for the first time that the newer pneumococcal virulence protein PepO activates host innate immune response partially through TLR2 and TLR4 signaling pathways.
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University Chongqing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University Chongqing, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Kang
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University Chongqing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yao
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University Chongqing, China.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University Chongqing, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University Chongqing, China.
authors.forename: Wenchun
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University Chongqing, China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University Chongqing, China.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University Chongqing, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D054360:Chemokine CXCL1 / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000378:metabolism; D010450:Endopeptidases / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology; D020381:Interleukin-17 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000472:pathogenicity*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D037521:Virulence Factors / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D054360:Chemokine CXCL1; D054357:Chemokine CXCL10; C475895:Cxcl1 protein, mouse; C485433:Cxcl10 protein, mouse; D020381:Interleukin-17; D015850:Interleukin-6; C498144:Rela protein, mouse; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D037521:Virulence Factors; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D010450:Endopeptidases; C445310:PepO protein, Streptococcus pneumoniae
keywords: PepO; Streptococcus pneumonia; TLR2; TLR4; innate immunity; signaling pathway