T cell expression of IL-18R and DR3 is essential for non-cognate stimulation of Th1 cells and optimal clearance of intracellular bacteria

PLoS Pathogens

Hope O’Donnell¹  Stephen J. McSorley¹  Oanh H. Pham¹  Renée M. Tsolis²  Tobias Kerrinnes²  Aymen Al-Shamkhani³ 

[1] Center for Comparative Medicine and Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America;Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Davis, California, United States of America;Faculty of Medicine, University of Southampton, Southampton, United Kingdom

关键词: T helper cells;    Salmonellosis;    Cytokines;    Chlamydia infection;    T cells;    Immune response;    Spleen;    Salmonella;   

DOI  :  10.1371/journal.ppat.1006566

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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-γ 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.

【 授权许可】

CC BY