%0 Journal Article
%T T cell expression of IL-18R and DR3 is essential for non-cognate stimulation of Th1 cells and optimal clearance of intracellular bacteria
%A Aymen Al-Shamkhani
%A Hope O¡¯Donnell
%A Oanh H. Pham
%A Ren¨¦e M. Tsolis
%A Stephen J. McSorley
%A Tobias Kerrinnes
%J -
%D 2017
%R 10.1371/journal.ppat.1006566
%X Th1 cells can be activated by TCR-independent stimuli, but the importance of this pathway in vivo and the precise mechanisms involved require further investigation. Here, we used a simple model of non-cognate Th1 cell stimulation in Salmonella-infected mice to examine these issues. CD4 Th1 cell expression of both IL-18R and DR3 was required for optimal IFN-¦Ă induction in response to non-cognate stimulation, while IL-15R expression was dispensable. Interestingly, effector Th1 cells generated by immunization rather than live infection had lower non-cognate activity despite comparable IL-18R and DR3 expression. Mice lacking T cell intrinsic expression of MyD88, an important adapter molecule in non-cognate T cell stimulation, exhibited higher bacterial burdens upon infection with Salmonella, Chlamydia or Brucella, suggesting that non-cognate Th1 stimulation is a critical element of efficient bacterial clearance. Thus, IL-18R and DR3 are critical players in non-cognate stimulation of Th1 cells and this response plays an important role in protection against intracellular bacteria
%K T helper cells
%K Salmonellosis
%K Cytokines
%K Chlamydia infection
%K T cells
%K Immune response
%K Spleen
%K Salmonella
%U https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006566