title: Antibody blocks acquisition of bacterial colonization through agglutination.
abstract: Invasive infection often begins with asymptomatic colonization of mucosal surfaces. A murine model of bacterial colonization with Streptococcus pneumoniae was used to study the mechanism for mucosal protection by immunoglobulin. In previously colonized immune mice, bacteria were rapidly sequestered within large aggregates in the nasal lumen. To further examine the role of bacterial agglutination in protection by specific antibodies, mice were passively immunized with immunoglobulin G (IgG) purified from antipneumococcal sera or pneumococcal type-specific monoclonal human IgA (hIgA1 or hIgA2). Systemically delivered IgG accessed the mucosal surface and blocked acquisition of colonization and transmission between littermates. Optimal protection by IgG was independent of Fc fragment and complement and, therefore, did not involve an opsonophagocytic mechanism. Enzymatic digestion or reduction of IgG before administration showed that protection required divalent binding that maintained its agglutinating effect. Divalent hIgA1 is cleaved by the pneumococcal member of a family of bacterial proteases that generate monovalent Fabα fragments. Thus, passive immunization with hIgA1 blocked colonization by an IgA1-protease-deficient mutant (agglutinated) but not the protease-producing wild-type parent (not agglutinated), whereas protease-resistant hIgA2 agglutinated and blocked colonization by both. Our findings highlight the importance of agglutinating antibodies in mucosal defense and reveal how successful pathogens evade this effect.
authors: Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: A M
authors: AM
authors: Roche
authors: Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: A L
authors: AL
authors: Richard
authors: 1] Mucosal and Vaccine Research Program Colorado (MAVRC), Division of Infectious Disease, University of Colorado Denver, Aurora, Colorado, USA [2] Denver Veterans Affairs Medical Center, Denver, Colorado, USA.
authors: J T
authors: JT
authors: Rahkola
authors: 1] Mucosal and Vaccine Research Program Colorado (MAVRC), Division of Infectious Disease, University of Colorado Denver, Aurora, Colorado, USA [2] Denver Veterans Affairs Medical Center, Denver, Colorado, USA.
authors: E N
authors: EN
authors: Janoff
authors: Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: J N
authors: JN
authors: Weiser
mesh_terms: D000371:Agglutination / Q000235:genetics / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics; D048708:Cell Growth Processes / Q000276:immunology; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D006801:Humans; D057131:Immune Evasion; D007070:Immunoglobulin A / Q000276:immunology / Q000378:metabolism*; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D009297:Nasal Mucosa / Q000276:immunology* / Q000382:microbiology; D010447:Peptide Hydrolases / Q000235:genetics; D011008:Pneumococcal Infections / Q000276:immunology* / Q000635:transmission; D013296:Streptococcus pneumoniae / Q000254:growth & development / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D010447:Peptide Hydrolases