PLoS Pathogens | |
T cell expression of IL-18R and DR3 is essential for non-cognate stimulation of Th1 cells and optimal clearance of intracellular bacteria | |
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
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
RO201902015821139ZK.pdf | 5222KB | download |