{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:47:57Z","timestamp":1790776077143,"version":"4.1.0"},"reference-count":37,"publisher":"Rockefeller University Press","issue":"9","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,8,25]]},"abstract":"<jats:p>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\u2013specific IgG2 antibodies. Depletion of IgG2 to O-antigen restores the ability of sera to kill strains with long-chain O-antigen. Patients with impaired serum-mediated killing of P. aeruginosa by IgG2 have poorer respiratory function than infected patients who do not produce inhibitory antibody. We suggest that excessive binding of IgG2 to O-antigen shields the bacterium from other antibodies that can induce complement-mediated killing of bacteria. As there is significant sharing of O-antigen structure between different Gram-negative bacteria, this IgG2-mediated impairment of killing may operate in other Gram-negative infections. These findings have marked implications for our understanding of protection generated by natural infection and for the design of vaccines, which should avoid inducing such blocking antibodies.<\/jats:p>","DOI":"10.1084\/jem.20132444","type":"journal-article","created":{"date-parts":[[2014,8,12]],"date-time":"2014-08-12T04:39:28Z","timestamp":1407818368000},"page":"1893-1904","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":86,"title":["Increased severity of respiratory infections associated with elevated anti-LPS IgG2 which inhibits serum bactericidal killing"],"prefix":"10.1084","volume":"211","author":[{"given":"Timothy J.","family":"Wells","sequence":"first","affiliation":[{"name":"Institute of Microbiology and Infection 1 , 2 , 3"},{"name":"School of Immunity and Infection 1 , 2 , 3"},{"name":"School Clinical and Experimental Medicine, University of Birmingham, Birmingham B15 2TT, England, UK 1 , 2 , 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