title: Interactions between Bordetella pertussis and the complement inhibitor factor H.
abstract: Bordetella pertussis causes whooping cough in humans, a highly contagious disease of the upper respiratory tract. An increase in cases of whooping cough in adolescents and adults in many countries has been reported, despite high immunization rates in children. To efficiently colonize the host the bacteria have to resist complement, the first defence line of innate immunity. B. pertussis has previously been shown to bind the classical pathway inhibitors C4b-binding protein and C1-inhibitor being thereby able to escape the classical pathway of complement. In this study recent clinical isolates of B. pertussis and B. parapertussis were found to survive alternative pathway attack in fresh non-immune serum better than the reference B. pertussis strain, Tohama I. By using adsorption assays, flow cytometry and a radioligand binding assay we observed that both B. pertussis and B. parapertussis bound the alternative pathway inhibitor factor H (FH) from normal human serum. The surface attached FH maintained its complement regulatory activity and promoted factor I-mediated cleavage of C3b. The main binding region was located to the C-terminal part of FH, into short consensus repeat domains 19-20. In contrast, the avian pathogen B. avium did not bind FH and was sensitive to the alternative pathway of human complement. In conclusion, the human pathogens B. pertussis and B. parapertussis are able to evade the alternative complement pathway by surface acquisition of the host complement regulator FH.
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Hanne
authors.initials: H
authors.lastname: Amdahl
authors.forename: Hanna
authors.initials: H
authors.lastname: Jarva
authors.forename: Marjo
authors.initials: M
authors.lastname: Haanperä
authors.forename: Jussi
authors.initials: J
authors.lastname: Mertsola
authors.forename: Qiushui
authors.initials: Q
authors.lastname: He
authors.forename: T Sakari
authors.initials: TS
authors.lastname: Jokiranta
authors.forename: Seppo
authors.initials: S
authors.lastname: Meri
mesh_terms: D001665:Binding Sites; D001798:Blood Proteins / Q000378:metabolism; D042483:Bordetella parapertussis / Q000166:cytology / Q000276:immunology; D001886:Bordetella pertussis / Q000166:cytology / Q000276:immunology*; D050716:Complement C4b-Binding Protein; D017242:Complement Factor H / Q000737:chemistry / Q000276:immunology*; D051056:Complement Inactivating Agents / Q000737:chemistry / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000378:metabolism; D006801:Humans; D050296:Microbial Viability; D011485:Protein Binding
chemical_list: D001798:Blood Proteins; C055609:C4BPA protein, human; D050716:Complement C4b-Binding Protein; D051056:Complement Inactivating Agents; D006649:Histocompatibility Antigens; C100631:factor H-related protein 1; D017242:Complement Factor H