Humanized nonobese diabetic-scid IL2rγnull mice are susceptible to lethal Salmonella Typhi infection
Humanized nonobese diabetic-scid IL2rγnull mice are susceptible to lethal Salmonella Typhi infection
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DOI：
10.1073/pnas.1005566107
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发表时间：
2010-08-31
影响因子：
11.1
通讯作者：
Fang, Ferric C.
中科院分区：
文献类型：
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作者：
Libby, Stephen J.;Brehm, Michael A.;Fang, Ferric C.
伤寒沙门氏菌（Salmonella enterica serovar Typhi）是伤寒的致病菌，它适应于人类宿主，不会在小鼠中致病。在这里，我们证明了S.伤寒可以在植入人造血干细胞的非肥胖糖尿病（NOD）-scid IL 2 r γ（null）小鼠（hu-SRC-SCID小鼠）中体内复制，以引起具有类似于人伤寒的病理和炎性细胞因子应答的致死性感染。相反，S.伤寒在非移植或免疫活性对照动物中不表现出净复制或引起疾病。在hu-SRC-SCID小鼠中筛选转座子库揭示了已知和先前未知的沙门氏菌毒力决定簇，包括沙门氏菌致病性岛1、2、3、4和6。我们的观察表明，人类免疫细胞的存在允许在体内复制的S。小鼠伤寒。hu-SRC-SCID小鼠为深入了解S.伤寒的发病机制及制订预防伤寒的策略。
Salmonella enterica serovar Typhi, the cause of typhoid fever, is host-adapted to humans and unable to cause disease in mice. Here, we show that S. Typhi can replicate in vivo in nonobese diabetic (NOD)-scid IL2r gamma(null) mice engrafted with human hematopoietic stem cells (hu-SRC-SCID mice) to cause a lethal infection with pathological and inflammatory cytokine responses resembling human typhoid. In contrast, S. Typhi does not exhibit net replication or cause illness in nonengrafted or immunocompetent control animals. Screening of transposon pools in hu-SRC-SCID mice revealed both known and previously unknown Salmonella virulence determinants, including Salmonella Pathogenicity Islands 1, 2, 3, 4, and 6. Our observations indicate that the presence of human immune cells allows the in vivo replication of S. Typhi in mice. The hu-SRC-SCID mouse provides an unprecedented opportunity to gain insights into S. Typhi pathogenesis and devise strategies for the prevention of typhoid fever.