Abstract
Surfactant protein A (SP-A) plays an important role in innate immune response and host defense against various microorganisms through opsonization and complement activation. To investigate the role of SP-A in non-typeable Haemophilus influenzae (NTHi)-induced acute otitis media, this study used wild type C57BL/6 (WT) and SP-A knockout (KO) mice. We divided mice into an infection group in which the middle ear (ME) was injected with NTHi and a control group that received the same treatment using normal saline. Mice were sacrificed on d 1, 3, and 7 after treatment. Temporal bone samples were fixed for histological, cellular, and molecular analyses. Ear washing fluid (EWF) was collected for culture and analyses of pro-inflammatory cytokines and inflammatory cells. SP-A-mediated bacterial aggregation and killing and phagocytosis by macrophages were studied in vitro. SP-A expression was detected in the ME and Eustachian tube mucosa of WT mice but not KO mice. After infection, KO mice showed more severe inflammation evidenced by increased ME mucosal thickness and inflammatory cell infiltration and higher NF-κB activation compared to WT mice. The levels of IL-6 and IL-1β in the EWF of infected KO mice were higher compared to infected WT mice on d 1. Our studies demonstrated that SP-A mediated NTHi aggregation and killing and enhanced bacterial phagocytosis by macrophages in vitro and modulated inflammation of the ME in otitis media in vivo.