TY - JOUR
T1 - Hyper innate responses in neonates lead to increased morbidity and mortality after infection
AU - Zhao, Jie
AU - Kwang, Dong Kim
AU - Yang, Xuanming
AU - Auh, Sogyong
AU - Fu, Yang Xin
AU - Tang, Hong
PY - 2008/5/27
Y1 - 2008/5/27
N2 - 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 (DGalN). However, we show that neonatal mice demonstrate much stronger inflammatory responses than adult mice in response to LPS 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-GalN to adult liver cells, rather than accurately reflecting the TLR response to LPS. 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 LPS. Therefore, neonates might suffer from the unleashed innate responses caused by an insufficient number of T cells, which leads to increased morbidity and mortality.
AB - 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 (DGalN). However, we show that neonatal mice demonstrate much stronger inflammatory responses than adult mice in response to LPS 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-GalN to adult liver cells, rather than accurately reflecting the TLR response to LPS. 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 LPS. Therefore, neonates might suffer from the unleashed innate responses caused by an insufficient number of T cells, which leads to increased morbidity and mortality.
UR - http://www.scopus.com/inward/record.url?scp=44949254925&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=44949254925&partnerID=8YFLogxK
U2 - 10.1073/pnas.0800152105
DO - 10.1073/pnas.0800152105
M3 - Article
C2 - 18490660
AN - SCOPUS:44949254925
SN - 0027-8424
VL - 105
SP - 7528
EP - 7533
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 21
ER -