Pneumococcal IgA1 protease subverts specific protection by human IgA1

• Published in: Mucosal immunology Vol. 7; no. 2; pp. 249 - 256
• Main Authors: Janoff, E N, Rubins, J B, Fasching, C, Charboneau, D, Rahkola, J T, Plaut, A G, Weiser, J N
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.03.2014
• Subjects: Animals; Disease Models, Animal; Humans; Immunoglobulin A - immunology; Immunoglobulin A - metabolism; Immunoglobulin G - blood; Immunoglobulin G - immunology; Mice; Phagocytosis - immunology; Pneumococcal Infections - immunology; Pneumococcal Infections - metabolism; Serine Endopeptidases - metabolism; Streptococcus pneumoniae - enzymology; Streptococcus pneumoniae - immunology
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/mi.2013.41

Bacterial immunoglobulin A1 (IgA1) proteases may sabotage the protective effects of IgA. In vitro, both exogenous and endogenously produced IgA1 protease inhibited phagocytic killing of Streptococcus pneumoniae by capsule-specific IgA1 human monoclonal antibodies (hMAbs) but not IgA2. These IgA1 proteases cleaved and reduced binding of the the effector Fcα1 heavy chain but not the antigen-binding F(ab)/light chain to pneumococcal surfaces. In vivo, IgA1 protease-resistant IgA2, but not IgA1 protease-sensitive IgA1, supported 60% survival in mice infected with wild-type S. pneumoniae. IgA1 hMAbs protected mice against IgA1 protease-deficient but not -producing pneumococci. Parallel mouse sera with human IgA2 showed more efficient complement-mediated reductions in pneumococci with neutrophils than did IgA1, particularly with protease-producing organisms. After natural human pneumococcal bacteremia, purified serum IgG inhibited IgA1 protease activity in 7 of 11 patients (64%). These observations provide the first evidence in vivo that IgA1 protease can circumvent killing of S. pneumoniae by human IgA. Acquisition of IgA1 protease-neutralizing IgG after infection directs attention to IgA1 protease both as a determinant of successful colonization and infection and as a potential vaccine candidate.