Abstract
Effective immunity against Bordetella pertussis is currently under discussion following the stacking evidence of pertussis resurgence in the vaccinated population. Natural immunity is more effective than vaccine-induced immunity indicating that knowledge on infection-induced responses may contribute to improve vaccination strategies. We applied a systems biology approach comprising microarray, flow cytometry and multiplex immunoassays to unravel the molecular and cellular signatures in unprotected mice and protected mice with infection-induced immunity, around a B. pertussis challenge. Pre-existing systemic memory Th1/Th17 cells, memory B-cells, and mucosal IgA specific for Ptx, Vag8, Fim2/3 were detected in the protected mice 56 days after an experimental infection. In addition, pre-existing high activity and reactivation of pulmonary innate cells such as alveolar macrophages, M-cells and goblet cells was detected. The pro-inflammatory responses in the lungs and serum, and neutrophil recruitment in the spleen upon an infectious challenge of unprotected mice were absent in protected mice. Instead, fast pulmonary immune responses in protected mice led to efficient bacterial clearance and harbored potential new gene markers that contribute to immunity against B. pertussis. These responses comprised of innate makers, such as Clca3, Retlna, Glycam1, Gp2, and Umod, next to adaptive markers, such as CCR6+ B-cells, CCR6+ Th17 cells and CXCR6+ T-cells as demonstrated by transcriptome analysis. In conclusion, besides effective Th1/Th17 and mucosal IgA responses, the primary infection-induced immunity benefits from activation of pulmonary resident innate immune cells, achieved by local pathogen-recognition. These molecular signatures of primary infection-induced immunity provided potential markers to improve vaccine-induced immunity against B. pertussis.
Highlights
The resurgence of pertussis in the vaccinated population prompts the necessity of more knowledge on effective immunity against Bordetella pertussis [1, 2]
This global health problem occurs after vaccination with acellular pertussis vaccines and whole-cell pertussis vaccines as recent data point out [3]. aPV-vaccinated individuals face waning immunity early after vaccination, since the vaccine-induced immunity lasts for only 4–12 years [4, 5] despite multiple booster vaccinations [6]
The immunity induced by a B. pertussis infection may provide crucial information for improving vaccine-induced immunity, since it provides important advantages compared to immunity induced by aPV or whole-cell pertussis vaccines (wPV)
Summary
The resurgence of pertussis in the vaccinated population prompts the necessity of more knowledge on effective immunity against Bordetella pertussis [1, 2]. The lung epithelial cells offer a first line of defense by secretion of anti-microbial peptides and pathogen recognition, and by interaction with the local innate immune cells [13] These innate immune cells include mucin-secreting goblet cells [14], alveolar macrophages [15] and the upper layer of the bronchus-associated lymphoid tissue (BALT) [16], that act in the same way as microfold (M)-cells [17], harbor functions, such as pathogen recognition and antigen-uptake. These pulmonary innate cells orchestrate the specific adaptive immune responses, such as mucosal IgA production and activation of tissue-resident B-cells and T-cells in the BALT [16]
Sign-in/Register to view highlights & summary 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.
