Haemophilus influenzae survival during complement-mediated attacks is promoted by Moraxella catarrhalis outer membrane vesicles

Moraxella catarrhalis causes respiratory tract infections in children and in adults with chronic obstructive pulmonary disease. It is often isolated as a copathogen with Haemophilus influenzae. The underlying mechanism for this cohabitation is unclear. Here, in clinical specimens from a patient with M. catarrhalis infection, we document that outer membrane vesicles (OMVs) carrying ubiquitous surface protein (Usp) A1 and UspA2 (hereafter, UspA1/A2) were secreted. Further analyses revealed that OMVs isolated in vitro also contained UspA1/A2, which mediate interactions with, among other proteins, the third component of the complement system (C3). OMVs from M. catarrhalis wild-type clinical strains bound to C3 and counteracted the complement cascade to a larger extent than did OMVs without UspA1/A2. In contrast, UspA1/A2-deficient OMVs were significantly weaker inhibitors of complement-dependent killing of H. influenzae. Thus, our results suggest that a novel strategy exists in which pathogens collaborate to conquer innate immunity and that the M. catarrhalis vaccine candidates UspA1/A2 play a major role in this interaction.