Hyper innate responses in neonates lead to increased morbidity and mortality after infection.
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-GalN). 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.
Zhao
Jie
J
Center for Infection and Immunity and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.
Kim
Kwang Dong
KD
Yang
Xuanming
X
Auh
Sogyong
S
Fu
Yang-Xin
YX
Tang
Hong
H
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D016207:Cytokines / Q000378:metabolism; D005688:Galactosamine / Q000276:immunology / Q000494:pharmacology; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000276:immunology / Q000494:pharmacology; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D051193:Toll-Like Receptors / Q000819:agonists / Q000378:metabolism*; D014777:Virus Diseases / Q000276:immunology*
D016207:Cytokines; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D005688:Galactosamine; D011070:Poly I-C