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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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 4

Pneumococcal carriage leads to increased systemic plasmablasts.

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Pneumococcal carriage leads to increased systemic plasmablasts. (A) Leve...
(A) Levels of 6B polysaccharide–specific, 15B polysaccharide–specific, pneumolysin derivative b–specific (Pneumolysin), or all plasmablasts among total B cells were measured from PBMCs collected at baseline (day –5) and at the time of biopsy (day 10 after inoculation). Box plots depicting median and interquartile ranges, with whiskers extending to 1.5× interquartile range or maximum value, and individual subjects are shown with carriage– in blue (n = 12) and carriage+ in red (n = 8). Paired samples are connected by dashed lines. *P < 0.05, **P < 0.01 by Wilcoxon’s test comparing a group to its baseline. (B) Levels of CCR10+ plasmablasts for 6B-specific and total plasmablasts measured from PBMCs collected at baseline (day –5) and at the time of biopsy (day 10 after inoculation [p.i.]). Box plots and individual subjects are depicted with carriage– in blue and carriage+ in red, with paired samples connected by dashed lines. **P < 0.01 by Wilcoxon’s test comparing a group to its baseline. (C) Correlations between fold-change in levels of 6B polysaccharide–specific and total plasmablasts between baseline and day 10 against levels of B cell clusters measured by CyTOF. PS, polysaccharide. Color and size of symbols reflect Spearman’s rho value. *P < 0.05, **P < 0.01 by Spearman’s test.