Humanized nonobese diabetic-scid IL2rγnull mice are susceptible to lethal Salmonella Typhi infection

被引：97

作者：

Libby, Stephen J. ^{[1
,2
]}

Brehm, Michael A. ^{[3
,4
]}

Greiner, Dale L. ^{[3
,4
]}

Shultz, Leonard D. ^{[5
]}

McClelland, Michael ^{[6
]}

Smith, Kelly D. ^{[1
,2
]}

Cookson, Brad T. ^{[1
,2
]}

Karlinsey, Joyce E. ^{[1
,2
]}

Kinkel, Traci L. ^{[1
,2
]}

Porwollik, Steffen ^{[6
]}

Canals, Rocio ^{[6
]}

Cummings, Lisa A. ^{[1
,2
]}

Fang, Ferric C. ^{[1
,2
]}

机构：

[1] Univ Washington, Sch Med, Dept Lab Med, Seattle, WA 98195 USA

[2] Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA

[3] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA

[4] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA

[5] Jackson Lab, Bar Harbor, ME 04609 USA

[6] Vaccine Res Inst San Diego, San Diego, CA 92121 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 35期

基金：

美国国家卫生研究院;

关键词：

pathogenesis; typhoid; virulence; animal model; bacterial infections; ENTERICA SEROVAR TYPHI; VI-ANTIGEN; REGULATORY SYSTEM; IMMUNE-RESPONSE; VIRULENCE GENE; TYPHIMURIUM; APOPTOSIS; SURVIVAL; PROTEIN; CYTOKINES;

D O I：

10.1073/pnas.1005566107

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：15589 / 15594

页数：6

共 70 条

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