bordetella pertussis commits human dendritic cells to promote a th1th17 response through the activity of adenylate cyclase toxin and mapk-pathways百日咳博德特氏菌提交人树突状细胞促进th1th17响应通过腺苷酸环化酶活性的毒素和mapk-pathways.pdfVIP

Bordetella pertussis Commits Human Dendritic Cells to Promote a Th1/Th17 Response through the Activity of Adenylate Cyclase Toxin and MAPK-Pathways 1. 1. 1 1 2¤ Giorgio Fedele , Fabiana Spensieri , Raffaella Palazzo , Maria Nasso , Gordon Yiu Chong Cheung , 2 1 John Graham Coote , Clara Maria Ausiello * ` 1 Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanita, Rome, Italy, 2 Division of Infection and Immunity, Institute of Biomedical and Life Sciences, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, United Kingdom Abstract The complex pathology of B. pertussis infection is due to multiple virulence factors having disparate effects on different cell types. We focused our investigation on the ability of B. pertussis to modulate host immunity, in particular on the role played by adenylate cyclase toxin (CyaA), an important virulence factor of B. pertussis. As a tool, we used human monocyte derived dendritic cells (MDDC), an ex vivo model useful for the evaluation of the regulatory potential of DC on T cell immune responses. The work compared MDDC functions after encounter with wild-type B. pertussis (BpWT) or a mutant lacking CyaA (BpCyaA2), or the BpCyaA2 strain supplemented with either the fully functional CyaA or a derivative, CyaA*, lacking adenylate cyclase activity. As a first step, MDDC maturation, cytokine production, and modulation of T helper cell polarization were evaluated. As a second step, engagement of Toll-like recept