Abstract
Worldwide resurgence of pertussis necessitates the need for improvement of pertussis vaccines and vaccination strategies. Since natural infections induce a longer-lasting immunity than vaccinations, detailed knowledge of the immune responses following natural infection can provide important clues for such improvement. The purpose was to elucidate the kinetics of the protective immune response evolving after experimental Bordetella pertussis (B. pertussis) infection in mice. Data were collected from (i) individual analyses, i.e. microarray, flow cytometry, multiplex immunoassays, and bacterial clearance; (ii) twelve time points during the infection; and (iii) different tissues involved in the immune responses, i.e. lungs, spleen and blood. Combined data revealed detailed insight in molecular and cellular sequence of events connecting different phases (innate, bridging and adaptive) of the immune response following the infection. We detected a prolonged acute phase response, broad pathogen recognition, and early gene signatures of subsequent T-cell recruitment in the lungs. Activation of particular transcription factors and specific cell markers provided insight into the time course of the transition from innate towards adaptive immune responses, which resulted in a broad spectrum of systemic antibody subclasses and splenic Th1/Th17 memory cells against B. pertussis. In addition, signatures preceding the local generation of Th1 and Th17 cells as well as IgA in the lungs, considered key elements in protection against B. pertussis, were established. In conclusion, molecular and cellular immunological processes in response to live B. pertussis infection were unraveled, which may provide guidance in selecting new vaccine candidates that should evoke local and prolonged protective immune responses.
Highlights
The gram-negative bacterium Bordetella pertussis, the causative agent of whooping cough, accounted for high mortality rates among infants in the pre-vaccine era
Mice previously infected with B. pertussis had developed sterilizing immunity, which clears the lungs in two days
Data sets from individual analytical platforms, such as microarray, flow cytometry, multiplex immunoassays, and colony counting, addressing different biological samples taken at multiple time points during the immune response were merged
Summary
The gram-negative bacterium Bordetella pertussis, the causative agent of whooping cough (pertussis), accounted for high mortality rates among infants in the pre-vaccine era. Whole cell and acellular vaccines have drastically decreased the number of cases [1]. Recently resurgence of pertussis in the vaccinated population has been observed in the USA [2,3] and in European countries [4,5]. Pertussis is still endemic, ranking in the top-ten of vaccine preventable diseases worldwide, according to the WHO. To improved diagnostics and public awareness, strain adaptation and waning immunity are thought to be responsible for this increase in disease cases [6]. A call for vaccines with improved efficacy is evident
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
