Streptococcus pneumoniae specific Th17 memory immunity provides cross protection against invasive pneumococcal diseases in mice. (IRC9P.701)

Abstract

Abstract Pneumonia caused by Streptococcus pneumoniae (Sp) remains a leading cause of serious illness and numerous deaths in children and elderly worldwide. Current pneumococcal vaccine is effective in preventing colonization by inducing serotype-specific antibodies. However, there is an increasing prevalence of infection by serotype strains not included in the vaccine; this highlights the need for a universal vaccine that protects against all serotypes. In current study, we found that mice intranasal immunized with Sp were protected against challenge with a different serotype Sp strain and cleared bacteria from the lung by day 2 post-challenge, and exhibited less apoptosis and tissue damage in lung. Sp infection in lung resulted in a tremendous CD4+T cell expansion and activation that consisted of mostly IL-17 producing Th17 cells but also IFNγ producing Th1 cells. Adoptive transfer of T cells from Sp immunized mice provided cross protection with a dominant Th17 recall response in the lung from donor CD4+ memory T cells. Furthermore, adoptive transfer of Sp specific CD4+ memory T cells provided cross protection against pneumonia and bacteremia, which can be blocked by IL-17 neutralizing antibody and transfer Sp memory CD4+ T cells from IL-17 knockout mice. Our results suggest that Sp memory Th17 cells played a key role in providing broad protective immunity against invasive Sp infection in a serotype independent manner.