Files
Abstract
Bordetella pertussis, the bacterial pathogen responsible for “whooping cough” causes an estimated 24 million cases of vaccine-preventable illness per year, resulting in an excess of 170,000 deaths annually. Due to these and other factors, both the CDC and NIH have listed Bp as a priority (re)emerging pathogen of high concern. Importantly, the incidence of whooping cough in nations with high vaccine coverage is on the rise, attributed to asymptomatic transmission that is enabled by the imperfect and waning immunity of current acellular pertussis (aP) vaccines. The inability of aP vaccines to generate sterilizing immunity in the nasopharynx has sparked a critical need to better understand the immune response to Bp at this initial site of infection, however, like many well-adapted pathogens, Bp has evolved complex mechanisms to modulate the host immune response. In an effort to better understand Bp suppression of host immunity, we have focused on a sigma factor (BtrS) that we have shown is critical to the regulation of Bordetella spp. immunomodulatory factors. Importantly, we observe that infection with an isogenic mutant lacking this regulator generates more robust and complete sterilizing immunity in the nasal cavity and lungs of convalescent mice. We also observed significant increases in CD4+ T cells in the nasal cavity and lungs, as well as elevated IgA titers in Bp∆btrS- convalescent mice following secondary challenge. The observation that the Bp mutant lacking this regulator (Bp∆btrS) induced more effective sterilizing anamnestic immunity in the nasalcavity presents the opportunity to study and understand both how Bp suppresses immunity and how enhanced protective immunity can be generated.