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Publication Detail
A novel Streptococcus pneumoniae human challenge model demonstrates Treg lymphocyte recruitment to the infection site
  • Publication Type:
    Journal article
  • Authors:
    Szylar G, Wysoczanski R, Marshall H, Marks DJB, José R, Ehrenstein ME, Brown JS
  • Publisher:
    Springer Science and Business Media LLC
  • Publication date:
    07/03/2022
  • Journal:
    Scientific Reports
  • Volume:
    12
  • Issue:
    1
  • Article number:
    3990
  • Status:
    Published
  • Country:
    England
  • PII:
    10.1038/s41598-022-07914-w
  • Language:
    English
  • Keywords:
    Diseases, Immunology, Medical research, Microbiology
  • Notes:
    Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Abstract
To investigate local tissue responses to infection we have developed a human model of killed Streptococcus pneumoniae challenge by intradermal injection into the forearm. S. pneumoniae intradermal challenge caused an initial local influx of granulocytes and increases in TNF, IL6 and CXCL8. However, by 48 h lymphocytes were the dominant cell population, mainly consisting of CD4 and CD8 T cells. Increases in local levels of IL17 and IL22 and the high proportion of CD4 cells that were CCR6+ suggested a significant Th17 response. Furthermore, at 48 h the CD4 population contained a surprisingly high proportion of likely memory Treg cells (CCR6 positive and CD45RA negative CD4+CD25highCD127low cells) at 39%. These results demonstrate that the intradermal challenge model can provide novel insights into the human response to S. pneumoniae and that Tregs form a substantial contribution of the normal human lymphocyte response to infection with this important pathogen.
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