Investigating the mechanisms of Bordetella pertussis-induced airway inflammation.

Bordetella pertussis is the etiological agent of pertussis, one of the most poorly controlled vaccine-preventable diseases in the world. Pertussis displays a range of severe pulmonary symptoms, including the hallmark paroxysmal cough (whooping cough) and can be fatal in infants. Further understanding of the molecular mechanisms of infection-associated exacerbation of airway inflammation and pathology is mandatory. To this purpose, we utilized a well-established model of in vitro monocyte-derived dendritic cells (MDDC) infection and analyzed by flow-cytometry, ELISA and RT-PCR the induction of diverse inflammatory mediators. B. pertussis induces the production by MDDC of Cyclooxygenase (COX)-2, prostaglandin E2 (PGE2), interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Indomethacin, a COX inhibitor impaired PGE2 and IL-6 but not TNF-α. MDDC infection with bacterial strains devoid of adenylate cyclase toxin (ACT) or pertussis toxin (PT) activity induced lower levels of COX-2 and PGE2 in MDDC. Worth of note, a neutralizing mAb directed against IL-10 reduced PGE2 production induced by B. pertussis. Overall, our findings appear to delineate the activation in B. pertussis-infected MDDC of a proinflammatory pathway encompassing COX-2 and PGE2, which is modulated by the activity of bacterial virulence factors and may contribute to inflammatory airway pathology. Future studies in this direction may disclose novel strategies of intervention aimed at alleviating the severe pathology experienced by infant pertussis patients.