The
adenylate cyclase (ACT) and the
pertussis (PT) toxins of Bordetella pertussis exert potent immunomodulatory activities that synergize to suppress host defense in the course of
whooping cough pathogenesis. We compared the mouse lung
infection capacities of B.
pertussis (Bp) mutants (Bp AC- or Bp PT-) producing enzymatically inactive
toxoids and confirm that ACT action is required for maximal bacterial proliferation in the first days of
infection, whereas PT action is crucial for persistence of B.
pertussis in mouse lungs. Despite accelerated and near complete clearance from the lungs by day 14 of
infection, the PT- bacteria accumulated within the lymphoid tissue of lung-draining mediastinal lymph nodes (mLNs). In contrast, the wild type or AC- bacteria colonized the lungs but did not enter into mLNs. Lung
infection by the PT- mutant triggered an early arrival of migratory conventional dendritic cells with associated bacteria into mLNs, where the PT- bacteria entered the T cell-rich paracortex of mLNs by day 5 and proliferated in clusters within the B-cell zone (cortex) of mLNs by day 14, being eventually phagocytosed by infiltrating neutrophils. Finally, only
infection by the PT- bacteria triggered an early production of anti-B.
pertussis serum
IgG antibodies already within 14 days of
infection. These results reveal that action of the
pertussis toxin blocks DC-mediated delivery of B.
pertussis bacteria into mLNs and prevents bacterial colonization of mLNs, thus hampering early adaptive immune response to B.
pertussis infection.