Mucin 1 (MUC1) is a cell-membrane associated glycoprotein that is widely expressed on epithelial cells lining the respiratory, gastro-intestinal and uro-genital tracts of the human body and on immune cells. This host factor confers protection against bacterial pathogens that invade these mucosal surfaces, primarily by functioning as an epithelial barrier. The current study was undertaken to investigate the role of MUC1 during infections caused by the respiratory pathogen Streptococcus pneumoniae.
Wildtype (WT) and MUC1-deficient (Muc1-/-) mice were infected intranasally with 106 S. pneumoniae D39 strain. At 16 hours post-infection, nasopharynx, lungs and blood were extracted from the infected mice and pneumococcal burden determined by colony-forming assay. Lungs were graded histologically for inflammation and cytokine profiles in the lungs were analyzed.
While there was no difference in pneumococcal colonization of the nasopharynx between WT and Muc1−/− mice, infected Muc1−/− mice showed high pneumococcal loads in their lungs. While only 1 out of 16 infected WT mice examined had bacteremia, 9 of 16 infected Muc1-/- mice showed bacteremia, indicating an invasive infection in the absence of MUC1. Infection in Muc1−/− mice was associated with an elevation in lung inflammation, with cellular recruitment especially of monocytes/macrophages. Using in vitro assays, it was demonstrated that macrophages from Muc1−/− mice exhibited a reduced capacity to phagocytose S. pneumoniae, contributing to establishment of bacteremia.
This study has identified a completely novel function of MUC1 on macrophages during severe pneumococcal infections. MUC1 has a protective function during pneumococcal pathogenesis, which is potentially mediated by facilitating macrophage phagocytosis.