<i>Haemophilus influenzae</i>Survival during Complement‐Mediated Attacks Is Promoted by<i>Moraxella catarrhalis</i>Outer Membrane Vesicles

Abstract

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.