期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 21, 页码 7528-7533出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0800152105
关键词
-
资金
- NCI NIH HHS [R01 CA115540, CA115540] Funding Source: Medline
- NIAID NIH HHS [AI062026, R01 AI062026] Funding Source: Medline
- NIDDK NIH HHS [DK58891, R01 DK058891] Funding Source: Medline
- NIGMS NIH HHS [T32 GM007281, 5 T32 GM07281] Funding Source: Medline
Neonates suffer high morbidity and mortality in. infection, presumably because of the lack of a fully developed adaptive and innate immune system. Evidence of poor innate responses in neonates has been shown by using a model that sensitizes the host to Toll-like receptor (TLR)-mediated inflammation with D-galactosamine (D-GaIN). However, we show that neonatal mice demonstrate much stronger inflammatory responses than adult mice in response to LIPS stimulation, and such hypersensitivity extends to other TLR agonists including actual viral infection. Our study reveals that the ensuing inflammatory reaction after D-GalN sensitization reflects preferential toxicity Of D-GaIN to adult liver cells, rather than accurately reflecting the TLR response to LIPS. We show further that an uncontrolled proinflammatory innate response due to inadequate T cells makes neonates more vulnerable to TLR agonists or viral infection. Remarkably, through transfer of T cells into neonates or depletion of T cells in adult mice, we show that T cells are sufficient and necessary to control the early inflammatory response to LIPS. Therefore, neonates might suffer from the unleashed innate responses caused by an insufficient number of T cells, which leads to increased morbidity and mortality.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据