Abstract
Whooping cough is a re-emerging respiratory tract infection. It has become clear that there is a need for better understanding of protective immune responses and variation between Bordetella pertussis strains to aid the development of improved vaccines. In order to survive in the host, B. pertussis has evolved mechanisms to evade complement-mediated killing, including the ability to bind complement-regulatory proteins. Here we evaluate the variation in interactions with the complement system among recently isolated strains. Isolates whose genomes appear highly similar and cluster together on a SNP-based dendrogram were found to vary significantly in resistance to complement-mediated killing and in the deposition of C3b/iC3b, C5b-9 and C1 esterase inhibitor (C1-INH). The key role of Vag8 as a receptor for C1-INH was confirmed and its expression was shown to vary in a panel of isolates. A Vag8 knockout mutant showed increased sensitivity to complement-mediated killing. Antibodies in convalescent sera blocked C1-INH binding to B. pertussis and may play an important role in natural immunity.
Highlights
Bordetella pertussis is the causative agent of whooping cough, a serious respiratory infectious disease in all age groups, with young infants at the greatest risk of severe disease
The lectin pathway (LP) is initiated via mannose-binding lectin (MBL) or ficolins forming a complex with the mannose-binding lectin-associated serine proteases on the pathogen surface and leads to the formation of the C3 convertase (C4b2a)
The differences in sensitivity to antibody-independent bactericidal killing were further characterised for strain Wellcome 28 and three UK 2012 isolates that were isolated in the same geographical region and that clustered together on a SNPbased dendrogram[23]
Summary
Bordetella pertussis is the causative agent of whooping cough, a serious respiratory infectious disease in all age groups, with young infants at the greatest risk of severe disease. The UK observed an increase in laboratory-confirmed pertussis cases from 2011 and experienced 9741 cases in 2012 with 14 infant deaths. Intact mucosal surfaces have about 10% of the complement concentration of serum and the amount increases during infection[7]. Evasion of this system is a survival strategy employed by many bacterial pathogens[8]. Cleavage of C5 leads to the deposition of C5a and the formation of the membrane attack complex, which is important in mediating killing. Antibody and complement-mediated opsonophagocytosis of B. pertussis has been demonstrated using sera from individuals with evidence of recent infection[10] and following vaccination[11, 12]. Antibody and complement interactions with B. pertussis are an important part of this picture and one that requires further characterisation
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