Open AccessEnhanced Susceptibility to Acute Pneumococcal Otitis Media in Mice Deficient in Complement C1qa, Factor B, and Factor B/C2
Author(s) -
Hua Hua Tong,
Yong Xing Li,
Gregory L. Stahl,
Joshua M. Thurman
Publication year - 2010
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.01012-09
Subject(s) - biology , streptococcus pneumoniae , otitis , complement (music) , complement factor b , factor h , immunology , microbiology and biotechnology , pneumococcal infections , complement factor i , factor (programming language) , acute otitis media , complement system , genetics , antibody , phenotype , antibiotics , gene , programming language , complementation , computer science
To define the roles of specific complement activation pathways in host defense againstStreptococcus pneumoniae in acute otitis media (AOM), we investigated the susceptibility to AOM in mice deficient in complement factor B and C2 (Bf/C2 −/ − ), C1qa (C1qa −/ − ), and factor B (Bf − / − ). Bacterial titers of bothS. pneumoniae serotype 6A and 14 in the middle ear lavage fluid samples fromBf/C2 −/ − ,Bf − / − , andC1qa −/ − mice were significantly higher than in samples from wild-type mice 24 h after transtympanical infection (P < 0.05) and remained persistently higher in samples fromBf/C2 −/ − mice than in samples from wild-type mice. Bacteremia occurred inBf/C2 −/ − ,Bf − / − , andC1qa −/ − mice infected with both strains, but not in wild-type mice. Recruitment of inflammatory cells was paralleled by enhanced production of inflammatory mediators in the middle ear lavage samples fromBf/C2 −/ − mice. C3b deposition on both strains was greatest for sera obtained from wild-type mice, followed byC1qa − / − andBf − / − mice, and least forBf/C2 − / − mice. Opsonophagocytosis and whole-blood killing capacity of both strains were significantly decreased in the presence of sera or whole blood from complement-deficient mice compared to wild-type mice. These findings indicate that both the classical and alternative complement pathways are critical for middle ear immune defense againstS. pneumoniae . The reduced capacity of complement-mediated opsonization and phagocytosis in the complement-deficient mice appears to be responsible for the impaired clearance ofS. pneumoniae from the middle ear and dissemination to the bloodstream during AOM.