Increased severity of respiratory infections associated with elevated anti-LPS IgG2 which inhibits serum bactericidal killing
Research output: Contribution to journal › Article
Colleges, School and Institutes
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 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.
|Number of pages||12|
|Journal||The Journal of Experimental Medicine|
|Publication status||Published - 25 Aug 2014|
- Antibodies, Blocking, Antibody-Dependent Enhancement, Blood Bactericidal Activity, Bronchiectasis, Complement System Proteins, Humans, Immunoglobulin G, O Antigens, Pseudomonas Infections, Pseudomonas aeruginosa, Respiratory Tract Infections