title: Essential role of factor B of the alternative complement pathway in complement activation and opsonophagocytosis during acute pneumococcal otitis media in mice.
abstract: We recently reported that the complement system plays a pivotal role in innate immune defense against Streptococcus pneumoniae during acute otitis media (OM) in mice. The current study was designed to determine which of the complement pathways are activated during acute pneumococcal OM and whether components of complement are expressed in the middle ear epithelium. Gene expression was determined by quantitative PCR, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining. We found that S. pneumoniae induced increased gene expression of factor B of the alternative complement pathway and C3 in mouse middle ear epithelium. Activation of factor B and C3 in the middle ear lavage fluids was significantly greater than in simultaneously obtained serum samples as determined by Western blotting. Using mice deficient in complement C1qa, factor B, and factor B/C2, we found that complement C3 activation and opsonophagocytosis of S. pneumoniae were greatly attenuated in factor B- and factor B/C2-deficient mice. These findings support the concept that local complement activation is an important host innate immune response and that activation of the alternative complement pathway represents one of the innate immune defense mechanisms against pneumococcal infection during the early stage of acute OM.
authors.affiliation: Department of Otolaryngology, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Yong Xing
authors.initials: YX
authors.lastname: Li
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Stahl
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Thurman
authors.forename: Yujuan
authors.initials: Y
authors.lastname: He
authors.forename: Hua Hua
authors.initials: HH
authors.lastname: Tong
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003167:Complement Activation; D003175:Complement C2 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D003176:Complement C3 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D011415:Complement Factor B / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D003170:Complement Pathway, Alternative; D004432:Ear, Middle / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D004848:Epithelium / Q000276:immunology; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010033:Otitis Media / Q000276:immunology*; D010587:Phagocytosis; D011008:Pneumococcal Infections / Q000276:immunology*; D016133:Polymerase Chain Reaction; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D003175:Complement C2; D003176:Complement C3; D011415:Complement Factor B