title: Adh enhances Actinobacillus pleuropneumoniae pathogenicity by binding to OR5M11 and activating p38 which induces apoptosis of PAMs and IL-8 release.
abstract: Members of the Trimeric Autotransporter Adhesin (TAA) family play a crucial role in the adhesion of Gram-negative pathogens to host cells, but the immunopathogenesis of TAAs remains unknown. Our previous studies demonstrated that Adh from Actinobacillus pleuropneumoniae (A. pleuropneumoniae) is required for full bacterial pathogenicity. Alveolar macrophages are the first line of defense against respiratory infections. This study compared the interactions between porcine alveolar macrophages (PAMs) and wild-type A. pleuropneumoniae (5b WT) or an Adh-deletion strain (5b ΔAdh) via gene microarray, immunoprecipitation and other technologies. We found that Adh was shown to interact with the PAMs membrane protein OR5M11, an olfactory receptor, resulting in the high-level secretion of IL-8 by activation of p38 MAPK signaling pathway. Subsequently, PAMs apoptosis via the activation of the Fax and Bax signaling pathways was observed, followed by activation of caspases 8, 9, and 3. The immunological pathogenic roles of Adh were also confirmed in both murine and piglets infectious models in vivo. These results identify a novel immunological strategy for TAAs to boost the pathogenicity of A. pleuropneumoniae. Together, these datas reveal the high versatility of the Adh protein as a virulence factor and provide novel insight into the immunological pathogenic role of TAAs.
authors.affiliation: College of Veterinary Medicine, JiLin University, Changchun, P. R. China.|College of Animal Science, Henan Institute of Science and Technology, Xinxiang, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, JiLin University, Changchun, P. R. China.
authors.forename: Wanhai
authors.initials: W
authors.lastname: Qin
authors.affiliation: Changchun University of Chinese Medicine, Changchun, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, JiLin University, Changchun, P. R. China.
authors.forename: Chuntong
authors.initials: C
authors.lastname: Bao
authors.affiliation: College of Veterinary Medicine, JiLin University, Changchun, P. R. China.
authors.forename: Hu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, JiLin University, Changchun, P. R. China.
authors.forename: Yanyi
authors.initials: Y
authors.lastname: Che
authors.affiliation: College of Veterinary Medicine, JiLin University, Changchun, P. R. China.
authors.forename: Changjiang
authors.initials: C
authors.lastname: Sun
authors.affiliation: College of Veterinary Medicine, JiLin University, Changchun, P. R. China.
authors.forename: Jingmin
authors.initials: J
authors.lastname: Gu
authors.affiliation: College of Veterinary Medicine, JiLin University, Changchun, P. R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Feng
authors.affiliation: College of Veterinary Medicine, JiLin University, Changchun, P. R. China.
authors.forename: Chongtao
authors.initials: C
authors.lastname: Du
authors.affiliation: College of Veterinary Medicine, JiLin University, Changchun, P. R. China.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Han
authors.affiliation: Section of Paediatrics, Imperial College London, London, UK.
authors.forename: Paul Langford
authors.initials: PL
authors.lastname: Richard
authors.affiliation: College of Veterinary Medicine, JiLin University, Changchun, P. R. China.
authors.forename: Liancheng
authors.initials: L
authors.lastname: Lei
mesh_terms: D016977:Actinobacillus pleuropneumoniae / Q000472:pathogenicity*; D018829:Adhesins, Bacterial / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D017353:Gene Deletion; D020869:Gene Expression Profiling; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation; D016209:Interleukin-8 / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology; D016676:Macrophages, Alveolar / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008807:Mice, Inbred BALB C; D046228:Microarray Analysis; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D018035:Receptors, Odorant / Q000378:metabolism*; D015398:Signal Transduction; D013552:Swine; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D016209:Interleukin-8; D043562:Receptors, G-Protein-Coupled; D018035:Receptors, Odorant; D037521:Virulence Factors; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D048051:p38 Mitogen-Activated Protein Kinases; D053453:Caspase 9