Immune Defense in Upper Airways: A Single-Cell Study of Pathogen-Specific Plasmablasts and Their Migratory Potentials in Acute Sinusitis and Tonsillitis

BACKGROUND: Despite the high frequency of upper respiratory tract (URT) infections and use of the nasal mucosa as route for vaccination, the local immune mechanism and dissemination of effector lymphocytes from the URT have been insufficiently characterized. To devise a single-cell approach for studying the mucosal immune response in the URT, we explored URT-originating B effector lymphocytes in the circulation of patients with one of two common respiratory infections, acute sinusitis or tonsillitis. METHODS: Patients with acute sinusitis (n = 13) or tonsillitis (n = 11) were investigated by ELISPOT for circulating pathogen-specific antibody-secreting cells (ASCs) of IgA, IgG and IgM isotypes approximately one week after the onset of symptoms. These cells’ potential to home into tissues was explored by assessing their expression of tissue-specific homing receptors α(4)β(7), L-selectin, and cutaneous lymphocyte antigen (CLA). RESULTS: Pathogen-specific ASCs were detected in the circulation of all patients, with a geometric mean of 115 (95% CI 46–282) /10(6) PBMC in sinusitis, and 48 (27–88) in tonsillitis. These responses were mainly dominated by IgG. In sinusitis α(4)β(7) integrin was expressed by 24% of the ASCs, L-selectin by 82%, and CLA by 21%. The proportions for tonsillitis were 15%, 80%, and 23%, respectively. Healthy individuals had no ASCs. CONCLUSIONS: URT infections–acute sinusitis and tonsillitis–both elicited a response of circulating pathogen-specific plasmablasts. The magnitude of the response was greater in sinusitis than tonsillitis, but the homing receptor profiles were similar. Human nasopharynx-associated lymphoid structures were found to disseminate immune effector cells with a distinct homing profile.