Defining mucosal immunity using mass cytometry following experimental human pneumococcal challenge

Abstract

1 Streptococcus pneumoniae (Spn) is a common cause of respiratory infection, but also frequently 2 colonises the nasopharynx in the absence of disease. We used mass cytometry to study immune 3 cells from nasal biopsy samples, collected following experimental human pneumococcal challenge, 4 in order to identify immunological changes that follow and control spn colonisation. Using 37 5 markers, we characterized 293 nasal immune cell clusters, of which 7 were associated with Spn 6 colonisation. B cell and CD8 + CD161 + T cell clusters were significantly higher in non-colonised than 7 in colonised subjects. Spn colonization led to recirculation of not only Spn-specific but also 8 aspecific nasal B cells. This associated with increased numbers of circulating plasmablasts and 9 increased antibody levels against the unrelated bacterium Haemophilus influenzae. In addition, we 10 demonstrated that baseline functionality of blood mucosal associated invariant T (MAIT) cells 11 associated with protection against Spn. These results identify new host-pathogen interactions at 12 the mucosa upon Spn colonisation.13 14