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

Jochems, Simon ORCID: https://orcid.org/0000-0002-4835-1032, de Ruiter, Karin, SolorzanoGonzalez, Carla ORCID: https://orcid.org/0000-0001-9129-5569, Voskamp, Astrid, Mitsi, Elena ORCID: https://orcid.org/0000-0001-7586-6050, Nikolaou, Elissavet, Carniel, Beatriz, Pojar, Sherin ORCID: https://orcid.org/0000-0002-7746-3279, German, Esther, Reiné, Jesús ORCID: https://orcid.org/0000-0001-7462-2054, Soares-Schanoski, Alessandra, Hill, Helen, Robinson, Rachel, Hyder-Wright, Angela, Weight, Caroline, Durrenberger, Pascal F., Heyderman, Robert, Gordon, Stephen ORCID: https://orcid.org/0000-0001-6576-1116, Smits, Hermelijn H., Urban, Britta ORCID: https://orcid.org/0000-0002-4197-8393, Rylance, Jamie ORCID: https://orcid.org/0000-0002-2323-3611, Collins, Andrea ORCID: https://orcid.org/0000-0002-4094-1572, Wilkie, Mark D., Lazarova, Lepa, Leong, Samuel ORCID: https://orcid.org/0000-0002-7213-0387, Yazdanbakhsh, Maria and Ferreira, Daniela ORCID: https://orcid.org/0000-0002-0594-0902 (2019) 'Innate and adaptive nasal mucosal immune responses following experimental human pneumococcal colonization'. Journal of Clinical Investigation, Vol 129, Issue 10, pp. 4523-4538.

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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 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.

Item Type:	Article
Subjects:	QW Microbiology and Immunology > Immunity by Type > QW 563 Local immunity QY Clinical Pathology > QY 4 General works WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 217 Pneumococcal infections
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology Clinical Sciences & International Health > Clinical Sciences Department Clinical Sciences & International Health > International Public Health Department Clinical Sciences & International Health > Malawi-Liverpool-Wellcome Programme (MLW)
Digital Object Identifer (DOI):	https://doi.org/10.1172/JCI128865
Depositing User:	Marie Hatton
Date Deposited:	02 Aug 2019 14:29
Last Modified:	13 Mar 2020 16:19
URI:	https://archive.lstmed.ac.uk/id/eprint/11342

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