biostudies-literatureWells TJMedical Research CouncilBiotechnology and Biological Sciences Research Council1893-904https://www.ebi.ac.uk/biostudies/studies/S-EPMC4144740biostudies-literatureUnknown211(9)Although specific antibody induced by pathogens or vaccines is a key component of protection against infectious threats, some viruses, such as dengue, induce antibody that enhances the development of infection. In contrast, antibody-dependent enhancement of bacterial infection is largely unrecognized. Here, we demonstrate that in a significant portion of patients with bronchiectasis and Pseudomonas aeruginosa lung infection, antibody can protect the bacterium from complement-mediated killing. Strains that resist antibody-induced, complement-mediated killing produce lipopolysaccharide containing O-antigen. The inhibition of antibody-mediated killing is caused by excess production of O-antigen-specific IgG2 antibodies. Depletion of IgG2 to O-antigen restores the ability of sera to kill straiThe Journal of experimental medicineIncreased severity of respiratory infections associated with elevated anti-LPS IgG2 which inhibits serum bactericidal killing.PMC4144740MC_PC_13057G0701275MR/L011263/1BB/L004461/1Sevastsyanovich YRCunningham AFBrowning DFHeath JNGoodall MO'Shea MKHenderson IRWhitters DCranston AMacLennan CAWells TJPravin JDe Soyza AStockley RAfalseIncreased severity of respiratory infections associated with elevated anti-LPS IgG2 which inhibits serum bactericidal killing.Although specific antibody induced by pathogens or vaccines is a key component of protection against infectious threats, some viruses, such as dengue, induce antibody that enhances the development of infection. In contrast, antibody-dependent enhancement of bacterial infection is largely unrecognized. Here, we demonstrate that in a significant portion of patients with bronchiectasis and Pseudomonas aeruginosa lung infection, antibody can protect the bacterium from complement-mediated killing. Strains that resist antibody-induced, complement-mediated killing produce lipopolysaccharide containing O-antigen. The inhibition of antibody-mediated killing is caused by excess production of O-antigen-specific IgG2 antibodies. Depletion of IgG2 to O-antigen restores the ability of sera to kill strai2014-01-01T00:00:00Z2014 Aug2025-05-31T23:13:02.973Z2025-05-31T23:13:02.973ZS-EPMC41447402511397510.1084/jem.20132444