期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 101, 期 46, 页码 16274-16279出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0406268101
关键词
mucosal immunity; pattern recognition; viral infection
资金
- NIAID NIH HHS [AI054395, R21 AI054395] Funding Source: Medline
Pattern recognition by Toll-like receptors (TLRs) is known to be important for the induction of dendritic cell (DC) maturation. DCS, in turn, are critically important in the initiation of T cell responses. However, most viruses do not infect DCs. This recognition system poses a biological problem in ensuring that most viral infections be detected by pattern recognition receptors. Furthermore, it is unknown what, if any, is the contribution of TLRs expressed by cells that are infected by a virus, versus TLRs expressed by DCs, in the initiation of antiviral adaptive immunity. Here we address these issues using a physiologically relevant model of mucosal infection with herpes simplex virus type 2. We demonstrate that innate immune recognition of viral infection occurs in two distinct stages, one at the level of the infected epithelial cells and the other at the level of the noninfected DCs. Importantly, both TLR-mediated recognition events are required for the induction of effector T cells. Our results demonstrate that virally infected tissues instruct DCs to initiate the appropriate class of effector T cell responses and reveal the critical importance of the stromal cells in detecting infectious agents through their own pattern recognition receptors.
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