Innate and adaptive nasal mucosal immune responses following experimental human pneumococcal colonization
Simon P. Jochems, … , Maria Yazdanbakhsh, Daniela M. Ferreira
Simon P. Jochems, … , Maria Yazdanbakhsh, Daniela M. Ferreira
Published October 1, 2019; First published July 30, 2019
Citation Information: J Clin Invest. 2019;129(10):4523-4538. https://doi.org/10.1172/JCI128865.
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Research Article Immunology Infectious disease

Innate and adaptive nasal mucosal immune responses following experimental human pneumococcal colonization

Abstract

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 CD161+CD8+ T cell clusters were significantly lower in colonized than in noncolonized 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 mucosa-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.

Authors

Simon P. Jochems, Karin de Ruiter, Carla Solórzano, Astrid Voskamp, Elena Mitsi, Elissavet Nikolaou, Beatriz F. Carniel, Sherin Pojar, Esther L. German, Jesús Reiné, Alessandra Soares-Schanoski, Helen Hill, Rachel Robinson, Angela D. Hyder-Wright, Caroline M. Weight, Pascal F. Durrenberger, Robert S. Heyderman, Stephen B. Gordon, Hermelijn H. Smits, Britta C. Urban, Jamie Rylance, Andrea M. Collins, Mark D. Wilkie, Lepa Lazarova, Samuel C. Leong, Maria Yazdanbakhsh, Daniela M. Ferreira

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Figure 3

Nasal B cells are depleted following pneumococcal carriage.

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Nasal B cells are depleted following pneumococcal carriage. (A) Heatmap ...
(A) Heatmap showing the expression of 37 markers for all B cell clusters. Clusters were ordered based on similarity, and a distance dendrogram is depicted. (B) The relative abundance for each of the 3 significantly higher clusters normalized to stromal cells is expressed on a log10 scale for carriage– (Spn–, blue, n = 12) and carriage+ (Spn+, red, n = 8) subjects. Box plots, depicting median and interquartile ranges, with whiskers extending to 1.5× interquartile range or maximum value, and individual subjects are shown. (C) Levels of CD19+ nasal B cells longitudinally measured by flow cytometry from minimally invasive nasal curettes in an independent cohort for carriage– (Spn–, blue, n = 52) and carriage+ (Spn+, red, n = 42) subjects. Mean and standard error of the mean of log2-transformed fold-change levels relative to baseline are shown. *P < 0.05 by Wilcoxon’s test compared with baseline with Bonferroni’s correction for comparing multiple time points.