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 July 30, 2019
Citation Information: J Clin Invest. 2019;129(10):e128865. 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 5

Increased MAIT cell responses associate with protection from carriage.

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Increased MAIT cell responses associate with protection from carriage. (...
(A) Heatmap showing the expression of 37 markers for each of the 4 CD8+ clusters that were significantly different between carriers and noncarriers. Nonsignificant CD8+ T clusters are not shown. Below the heatmap, the abundance for each of the significantly higher clusters normalized to stromal cells is expressed on a log10 scale for carriage– (blue) and carriage+ (red) subjects. Box plots depicting median and interquartile ranges, with whiskers extending to 1.5× interquartile range or maximum value, and individual subjects are depicted. (B) Representative flow cytometry contour plot of CD69+CD8+ and CD69–CD8+ T cells, showing CD103 and CD49a tissue-resident marker expression on nasal biopsy cells (n = 4). (C) Representative flow cytometry contour plot of unstimulated nasal biopsy cells, and nasal biopsy cells and PBMCs stimulated overnight with PMA and ionomycin (PI) to assess functional capacity (n = 4). (D) TNF-α, IFN-γ, and IL-17A production by CD8+ MAIT cells (CD161+TCRvα7.2+) after 3-day in vitro stimulation with heat-inactivated pneumococcus (HI-Spn) or left unstimulated for carriage– (blue, n = 14) and carriage+ (red, n = 8) subjects in PBMCs collected at baseline. Box plots and individual subjects, connected by dashed lines, are shown. **P < 0.01, ***P < 0.001 by Wilcoxon’s test. (E) Correlations between the difference in cytokine production (total of TNF-α and IFN-γ) by MAIT cells in vitro stimulated with HI-Spn or left unstimulated against CD161+CD8+ T cell clusters measured by CyTOF (n = 20). Color and size of symbols reflect Spearman’s rho value. *P < 0.05 by Spearman’s test.