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Streptococcus pneumoniae (Spn) is a common cause of respiratory infection, but also frequently colonizes the nasopharynx in the absence of disease. We used mass cytometry to study immune cells from nasal biopsy samples collected following experimental human pneumococcal challenge in order to identify immunological mechanisms of control of Spn colonization. Using 37 markers, we characterized 293 nasal immune cell clusters, of which 7 were associated with Spn colonization. B cell and CD8+CD161+ T cell clusters were significantly lower in colonized than in non-colonized subjects. By following a second cohort before and after pneumococcal challenge we observed that B cells were depleted from the nasal mucosa upon Spn colonization. This associated with an expansion of Spn polysaccharide-specific and total plasmablasts in blood. Moreover, increased responses of blood mucosal associated invariant T (MAIT) cells against in vitro stimulation with pneumococcus prior to challenge associated with protection against establishment of Spn colonization and with increased mucosal MAIT cell populations. These results implicate MAIT cells in the protection against pneumococcal colonization and demonstrate that colonization affects mucosal and circulating B cell populations.

Original publication

DOI

10.1172/JCI128865

Type

Journal article

Journal

J Clin Invest

Publication Date

30/07/2019

Volume

129

Pages

4523 - 4538

Keywords

B cells, Bacterial infections, Immunology, Infectious disease, Adaptive Immunity, Adult, B-Lymphocytes, CD8-Positive T-Lymphocytes, Female, Humans, Immunity, Innate, Immunity, Mucosal, Male, Nasal Mucosa, Pneumococcal Infections, Streptococcus pneumoniae