The Role of Iron in the Susceptibility of Neonatal Mice to Escherichia coli K1 Sepsis

被引:16
作者
Michels, Kathryn R. [1 ]
Lambrecht, Nathalie J. [2 ]
Lv, William F. Carson [1 ,5 ]
Schaller, Matthew A. [1 ,6 ]
Lukacs, Nicholas W. [1 ,3 ]
Bermick, Jennifer R. [4 ]
机构
[1] Univ Michigan, Sch Publ Hlth, Dept Pathol, Michigan Med, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Sch Publ Hlth, Dept Nutr Sci, Ann Arbor, MI 48109 USA
[3] Michigan Med, Mary H Weiser Food Allergy Ctr, Dept Pediat, Ann Arbor, MI 48109 USA
[4] Michigan Med, Dept Pediat, Div Neonatal Perinatal Med, Ann Arbor, MI 48109 USA
[5] Compass Therapeut, Cambridge, MA USA
[6] Univ Florida, Sch Med, Gainesville, FL USA
基金
美国国家卫生研究院;
关键词
sepsis; E; coli; neonatal; immunology; nutritional immunity; pediatrics; BOVINE LACTOFERRIN SUPPLEMENTATION; LATE-ONSET SEPSIS; INNATE IMMUNE; HOMEOSTASIS; DEFICIENCY; ABSORPTION; RESPONSES; GROWTH; CELLS;
D O I
10.1093/infdis/jiz282
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Sepsis from Escherichia coli expressing the K1 antigen is a leading cause of death in neonates. In a murine model, E. coli K1 grew rapidly in the peritoneal cavity of neonatal mice, causing fatal disease. In contrast, adult mice cleared the infection. Neonatal mice mounted a rapid and equivalent antimicrobial immune response compared to adult mice. Interestingly, peritoneal fluid from neonatal mice contained significantly more total iron than that of adult mice, which was sufficient to support enhanced E. coli growth. Transient iron overload in adult mice infected with E. coli resulted in 100% mortality. Maternal diet-induced mild iron deficiency decreased offspring peritoneal iron, decreased bacterial growth, and conferred protection against sepsis. Taken together, neonatal susceptibility to E. coli K1 sepsis is enhanced by a localized excess of peritoneal iron that allows for unchecked bacterial growth. Targeting this excess iron may provide a new therapeutic target in human patients.
引用
收藏
页码:1219 / 1229
页数:11
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