Abstract
Vaccines against pertussis have been available for more than 60 years. Nonetheless, this highly contagious disease is reemerging even in countries with high vaccination coverage. Genetic changes of Bordetella pertussis over time have been suggested to contribute to the resurgence of pertussis, as these changes may favor escape from vaccine-induced immunity. Nonetheless, studies on the effects of these bacterial changes on the immune response are limited. Here, we characterize innate immune recognition and activation by a collection of genetically diverse B. pertussis strains isolated from Dutch pertussis patients before and after the introduction of the pertussis vaccines. For this purpose, we used HEK-Blue cells transfected with human pattern recognition receptors TLR2, TLR4, NOD2 and NOD1 as a high throughput system for screening innate immune recognition of more than 90 bacterial strains. Physiologically relevant human monocyte derived dendritic cells (moDC), purified from peripheral blood of healthy donors were also used. Findings indicate that, in addition to inducing TLR2 and TLR4 signaling, all B. pertussis strains activate the NOD-like receptor NOD2 but not NOD1. Furthermore, we observed a significant increase in TLR2 and NOD2, but not TLR4, activation by strains circulating after the introduction of pertussis vaccines. When using moDC, we observed that the recently circulating strains induced increased activation of these cells with a dominant IL-10 production. In addition, we observed an increased expression of surface markers including the regulatory molecule PD-L1. Expression of PD-L1 was decreased upon blocking TLR2. These in vitro findings suggest that emerging B. pertussis strains have evolved to dampen the vaccine-induced inflammatory response, which would benefit survival and transmission of this pathogen. Understanding how this disease has resurged in a highly vaccinated population is crucial for the design of improved vaccines against pertussis.
Highlights
Bordetella pertussis is a human-specific Gram-negative bacterium and the causative agent of whooping cough, known as pertussis
Bordetella pertussis strains isolated from patients after the introduction of pertussis vaccination induce increased activation of human TLR2 and
In order to determine whether these strains induced TLR2, TLR4, NOD2 and
Summary
Bordetella pertussis is a human-specific Gram-negative bacterium and the causative agent of whooping cough, known as pertussis. This highly contagious disease of the upper respiratory tract can be fatal in unvaccinated infants and is the cause of persistent cough among older children and adults [1]. Cases of pertussis have increased in the past three decades [7]. Possible explanations for this resurgence include improved diagnosis, increased awareness, waning of vaccine-induced immunity and genetic changes of B. pertussis (reviewed in [8]).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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
