A Novel Streptococcus Pneumoniae Human Challenge Model Demonstrates Treg Lymphocyte Recruitment to the Infection Site

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 CD4CD25CD127 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.