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.
[1]Ohio State Univ, Dept Otolaryngol, Coll Med & Publ Hlth, Columbus, OH 43210 USA.
[2]Harvard Univ, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med, Brigham & Womens Hosp,Med Sch, Boston, MA 02115 USA.
[3]Univ Colorado Denver, Dept Med, Aurora, CO 80045 USA.
[4]Fudan Univ, Hua Shan Hosp, Dept Infect Dis, Shanghai 200433, Peoples R China.
[5]Chongqing Med Univ, Dept Clin Lab Med, Chongqing, Peoples R China.
(8.0+极速模式)