Pertussis toxin-dependent and -independent protection by Bordetella pertussis against influenza.

Bacterial-viral co-infections are frequent, but their reciprocal effects are not well understood. Here, we examined the effect Bordetella pertussis infection and the role of pertussis toxin (PT) on influenza A virus (IAV) infection and disease. In C57BL/6J mice, prior nasal administration of virulent B. pertussis BPSM and PT-deficient BPRA provided effective and sustained protection from IAV-induced mortality. However, BPSM or BPRA administered together with purified PT (BPRA + PT) had a stronger protective effect on weight loss compared to BPRA alone, reduced the viral load, and induced IL-17A in the lungs. In IL-17 mice, BPSM- and BPRA + PT-mediated protection against viral replication was abolished, while BPSM, BPRA and BPRA + PT provided similar levels of protection against IAV-induced mortality and weight loss. In conclusion, B. pertussis infection protects against influenza by two mechanisms: one reducing viral replication depending on PT and IL-17, and the other, independently of PT and IL-17, resulting in protection against influenza disease without reducing the viral load.