Hyper innate responses in neonates lead to increased morbidity and mortality after infection

Jie Zhao, Dong Kim Kwang, Xuanming Yang, Sogyong Auh, Yang Xin Fu, Hong Tang

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7528-7533
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number21
DOIs
StatePublished - May 27 2008

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Toll-Like Receptors
Morbidity
T-Lymphocytes
Mortality
Infection
Virus Diseases
Galactosamine
Immune System
Hypersensitivity
Inflammation
Liver

ASJC Scopus subject areas

  • General

Cite this

Hyper innate responses in neonates lead to increased morbidity and mortality after infection. / Zhao, Jie; Kwang, Dong Kim; Yang, Xuanming; Auh, Sogyong; Fu, Yang Xin; Tang, Hong.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 21, 27.05.2008, p. 7528-7533.

Research output: Contribution to journalArticle

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