age-dependent maturation of toll-like receptor-mediated cytokine responses in gambian infants年龄相关性成熟toll样受体介导的细胞因子反应在冈比亚的婴儿.pdfVIP

Age-Dependent Maturation of Toll-Like Receptor- Mediated Cytokine Responses in Gambian Infants 1,2 3 1 1 1 1 Sarah Burl *, John Townend , Jainaba Njie-Jobe , Momodou Cox , Uche J. Adetifa , Ebrima Touray , 4 4 1,2 1 1 Victoria J. Philbin , Christy Mancuso , Beate Kampmann , Hilton Whittle , Assan Jaye , Katie L. Flanagan1., Ofer Levy4. 1 Infant Immunology, Medical Research Council (UK) The Gambia, Fajara, The Gambia, 2 Department of Paediatrics, Imperial College London, Paddington, London, United Kingdom, 3 Statistics Department, Medical Research Council (UK) The Gambia, Fajara, The Gambia, 4 Division of Infectious Diseases, Department of Medicine, Children’s Hospital Boston and Harvard Medical School, Boston, Massachusetts, United States of America Abstract The global burden of neonatal and infant mortality due to infection is staggering, particularly in resource-poor settings. Early childhood vaccination is one of the major interventions that can reduce this burden, but there are specific limitations to inducing effective immunity in early life, including impaired neonatal leukocyte production of Th1-polarizing cytokines to many stimuli. Characterizing the ontogeny of Toll-like receptor (TLR)-mediated innate immune responses in infants may shed light on susceptibility to infection in this vulnerable age group, and provide insights into TLR agonists as candidate adjuvants for improved neonatal vaccines. As little is known about the leukocyte responses of infants in resource-poor settings, we characterized production of Th1-, Th2-, and anti-inflammatory-