Abstract
Whooping cough, caused by Bordetella pertussis, has resurged and presents a global health burden worldwide. B. pertussis strains unable to produce the acellular pertussis vaccine component pertactin (Prn), have been emerging and in some countries represent up to 95% of recent clinical isolates. Knowledge on the effect that Prn deficiency has on infection and immunity to B. pertussis is crucial for the development of new strategies to control this disease. Here, we characterized the effect of Prn production by B. pertussis on human and murine dendritic cell (DC) maturation as well as in a murine model for pertussis infection. We incubated human monocyte-derived DCs (moDCs) with multiple isogenic Prn knockout (Prn-KO) and corresponding parental B. pertussis strains constructed either in laboratory reference strains with a Tohama I background or in a recently circulating clinical isolate. Results indicate that, compared to the parental strains, Prn-KO strains induced an increased production of pro-inflammatory cytokines by moDCs. This pro-inflammatory phenotype was also observed upon stimulation of murine bone marrow-derived DCs. Moreover, RNA sequencing analysis of lungs from mice infected with B. pertussis Prn-KO revealed increased expression of genes involved in cell death. These in vitro and in vivo findings indicate that B. pertussis strains which do not produce Prn induce a stronger pro-inflammatory response and increased cell death upon infection, suggesting immunomodulatory properties for Prn.
Highlights
Introduction Bordetella pertussis is aGram-negative respiratory pathogen that causes pertussis, known as whooping cough, a vaccine-preventable disease
The vaccine strains carry the ptxP2 and ptxP1 alleles as opposed to the ptxP3 allele which is currently carried by over 90% of the circulating strains worldwide[27]. Another striking and most recent feature is the loss of production of antigens that are present in the acellular vaccines (ACV)
In ACV-using countries, such as Australia and the United States of America, over 80% of B. pertussis strains isolated from patients no longer produce Prn[6,28]
Summary
Gram-negative respiratory pathogen that causes pertussis, known as whooping cough, a vaccine-preventable disease. Pertussis has been re-emerging in many countries in recent decades and remains a public health problem[1]. This highly contagious respiratory disease can be life threatening in unvaccinated infants and causes significant morbidity across all age groups[2]. Towards controlling this disease, two different types of pertussis vaccines are licensed, namely whole cell vaccines (WCV).
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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
