title: Role of complement in host defense against pneumococcal otitis media.
abstract: Strategies to limit complement deposition on Streptococcus pneumoniae are established as virulence features for invasive disease, but their role in respiratory tract infection requires further analysis. We evaluated complement C3 protein deposition on discordant S. pneumoniae isolates of the same serotype (6A) and their capacity to cause nasopharyngeal (NP) colonization and experimental otitis media (EOM) in an animal model. We compared C3 binding to five 6A isolates from asymptomatic NP carriers with five 6A strains that caused invasive disease, and we observed less C3 ( approximately 10-fold less fluorescence) binding to invasive isolates. We selected two high-level C3-binding carriage and two low-level C3-binding invasive 6A isolates for further study. In the EOM model, 11/12 (92%) ears challenged with a low-level C3-binding 6A strain became infected. Only 2/8 (25%) ears challenged with the discordant high-level C3-binding 6A isolate developed disease (P = 0.005). Results with the second discordant 6A isolate pair were comparable. Cobra venom factor (CoVF) treatment, which depletes C3 and consumes complement, restored virulence of the high-level C3-binding strain; 8/8 (100%) ears in CoVF-treated animals developed EOM compared to only 25% of ears in naïve animals (P = 0.007). These studies demonstrate the critical role for complement evasion in pneumococcal EOM. Colonization with carriage isolates that bound high levels of C3 caused EOM in fewer animals compared to low-level C3-binding invasive strains. Thus, limiting C3 deposition on the surface of S. pneumoniae correlates with increased incidence of EOM following NP colonization and barotrauma in the animal model.
authors.affiliation: Section of Pediatric Infectious Diseases, Maxwell Finland Laboratory for Infectious Diseases, Boston Medical Center, Boston, Massachusetts 02118, USA. vishakha.sabharwal@bmc.org
authors.forename: Vishakha
authors.initials: V
authors.lastname: Sabharwal
authors.forename: Sanjay
authors.initials: S
authors.lastname: Ram
authors.forename: Marisol
authors.initials: M
authors.lastname: Figueira
authors.forename: In Ho
authors.initials: IH
authors.lastname: Park
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Pelton
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002682:Chinchilla; D003167:Complement Activation / Q000276:immunology; D003176:Complement C3 / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D009305:Nasopharynx / Q000276:immunology / Q000382:microbiology; D010033:Otitis Media / Q000276:immunology*; D011008:Pneumococcal Infections / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000472:pathogenicity*
chemical_list: D003176:Complement C3