<i>Bordetella pertussis</i> pertactin knock-out strains reveal immunomodulatory properties of this virulence factor

Whooping cough, caused by <i>Bordetella pertussis</i>, has resurged and presents a global health burden worldwide. <i>B. pertussis</i> 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 <i>B. pertussis</i> is crucial for the development of new strategies to control this disease. Here, we characterized the effect of Prn production by <i>B. pertussis</i> 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 <i>B. pertussis</i> 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 <i>B. pertussis</i> Prn-KO revealed increased expression of genes involved in cell death. These in vitro and in vivo findings indicate that <i>B. pertussis</i> strains which do not produce Prn induce a stronger pro-inflammatory response and increased cell death upon infection, suggesting immunomodulatory properties for Prn.