Absence of functional Hfe protects mice from invasive Salmonella enterica Serovar Typhimurium infection via induction of lipocalin-2

被引：131

作者：

Nairz, Manfred ^{[1
,2
]}

Theurl, Igor ^{[1
,2
]}

Schroll, Andrea ^{[1
,2
]}

Theurl, Milan ^{[1
,2
,3
]}

Fritsche, Gernot ^{[1
,2
]}

Lindner, Ewald ^{[1
,2
]}

Seifert, Markus ^{[1
,2
]}

Crouch, Marie-Laure V. ^{[4
]}

Hantke, Klaus ^{[5
]}

Akira, Shizuo ^{[6
,7
]}

Fang, Ferric C. ^{[4
,8
]}

Weiss, Guenter ^{[1
,2
]}

机构：

[1] Med Univ Innsbruck, Dept Internal Med 1, A-6020 Innsbruck, Austria

[2] Med Univ Innsbruck, Dept Clin Immunol & Infect Dis, A-6020 Innsbruck, Austria

[3] Med Univ Innsbruck, Dept Ophthalmol, A-6020 Innsbruck, Austria

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

[5] Univ Tubingen, Dept Microbiol Membrane Physiol, Tubingen, Germany

[6] Osaka Univ, Dept Host Def, Suita, Osaka 565, Japan

[7] Sci & Technol Corp, Osaka, Japan

[8] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA

来源：

BLOOD | 2009年 / 114卷 / 17期

关键词：

HUMAN MONOCYTIC CELLS; HEREDITARY HEMOCHROMATOSIS; INTERFERON-GAMMA; IRON HOMEOSTASIS; HEPCIDIN EXPRESSION; MYCOBACTERIUM-TUBERCULOSIS; NATURAL-RESISTANCE; DOWN-REGULATION; MACROPHAGES; RECEPTOR;

D O I：

10.1182/blood-2009-05-223354

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Mutations of HFE are associated with hereditary hemochromatosis, but their influence on host susceptibility to infection is incompletely understood. We report that mice lacking one or both Hfe alleles are protected from septicemia with Salmonella Typhimurium, displaying prolonged survival and improved control of bacterial replication. This increased resistance is paralleled by an enhanced production of the enterochelin-binding peptide lipocalin-2 (Lcn2), which reduces the availability of iron for Salmonella within Hfe-deficient macrophages. Accordingly, Hfe(-/-)Lcn2(-/-) macrophages are unable to efficiently control the infection or to withhold iron from intracellular Salmonella. Correspondingly, the protection conferred by the Hfe defect is abolished in Hfe(-/-) mice infected with enterochelin-deficient Salmonella as well as in Hfe(-/-)Lcn2(-/-) mice infected with wildtype bacteria. Thus, by induction of the iron-capturing peptide Lcn2, absence of functional Hfe confers host resistance to systemic infection with Salmonella, thereby providing an evolutionary advantage which may account for the high prevalence of genetic hemochromatosis. (Blood. 2009;114:3642-3651)

引用

页码：3642 / 3651

页数：10

共 56 条

[21] Natural resistance to infection with intracellular pathogens: The Nramp1 protein is recruited to the membrane of the phagosome [J].