Interferon-gamma promotes iron export in human macrophages to limit intracellular bacterial replication.
Interferon-gamma promotes iron export in human macrophages to limit intracellular bacterial replication.
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DOI：
10.1371/journal.pone.0240949
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Quinn F
中科院分区：
文献类型：
--
作者：
Abreu R;Essler L;Giri P;Quinn F
2018年，沙门氏菌病和李斯特菌病加在一起占美国食源性疾病的三分之一以上，占胃肠道疾病住院人数的近一半，而结核病困扰着全球1000多万人，导致近200万人死亡。无论单核细胞增生性李斯特氏菌、肠沙门氏菌和结核分枝杆菌之间的内在毒力差异如何，这些胞内病原体都具有在巨噬细胞和其他细胞内生存和存活的能力，并在富铁的环境中茁壮成长。干扰素-γ是机体抵抗细胞内病原体的中枢细胞因子，可促进巨噬细胞中铁的输出。我们假设干扰素-γ降低了细胞内病原体对铁的利用率，从而限制了这些细胞的复制。在这项研究中，我们发现干扰素-γ调节铁相关蛋白海普西丁、铁蛋白和铁蛋白的表达，从而诱导巨噬细胞铁输出。单核细胞增多性李斯特菌、肠杆菌和结核分枝杆菌感染可显著诱导人巨噬细胞中铁的滞留。相反，干扰素-γ显著减少肠杆菌和结核分枝杆菌感染的巨噬细胞的海普西丁的分泌。同样，干扰素-γ激活的巨噬细胞即使在感染单核细胞增生性乳杆菌后也比未经处理的对照组表达更高的铁孔蛋白水平；细菌感染大大下调了铁孔蛋白的表达。总的来说，干扰素-γ显著抑制病原体相关的巨噬细胞内铁的隔离，从而通过减少铁的可获得性来抑制细胞内细菌病原体的生长。
Salmonellosis and listeriosis together accounted for more than one third of foodborne illnesses in the United States and almost half the hospitalizations for gastrointestinal diseases in 2018 while tuberculosis afflicted over 10 million people worldwide causing almost 2 million deaths. Regardless of the intrinsic virulence differences among Listeria monocytogenes, Salmonella enterica and Mycobacterium tuberculosis, these intracellular pathogens share the ability to survive and persist inside the macrophage and other cells and thrive in iron rich environments. Interferon-gamma (IFN-γ) is a central cytokine in host defense against intracellular pathogens and has been shown to promote iron export in macrophages. We hypothesize that IFN-γ decreases iron availability to intracellular pathogens consequently limiting replication in these cells. In this study, we show that IFN-γ regulates the expression of iron-related proteins hepcidin, ferroportin, and ferritin to induce iron export from macrophages. Listeria monocytogenes, S. enterica, and M. tuberculosis infections significantly induce iron sequestration in human macrophages. In contrast, IFN-γ significantly reduces hepcidin secretion in S. enterica and M. tuberculosis infected macrophages. Similarly, IFN-γ-activated macrophages express higher ferroportin levels than untreated controls even after infection with L. monocytogenes bacilli; bacterial infection greatly down-regulates ferroportin expression. Collectively, IFN-γ significantly inhibits pathogen-associated intracellular iron sequestration in macrophages and consequently retards the growth of intracellular bacterial pathogens by decreasing iron availability.
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影响因子：
30.3
作者：
Arezes J;Jung G;Gabayan V;Valore E;Ruchala P;Gulig PA;Ganz T;Nemeth E;Bulut Y
通讯作者：
Bulut Y
影响因子：
29
作者：
Drakesmith H;Nemeth E;Ganz T
通讯作者：
Ganz T
影响因子：
6.4
作者：
Bao, S;Beagley, KW;Husband, AJ
通讯作者：
Husband, AJ
影响因子：
4.6
作者：
Abreu R;Essler L;Loy A;Quinn F;Giri P
通讯作者：
Giri P
DOI：
10.1073/pnas.97.3.1252
发表时间：
2000-02-01
影响因子：
11.1
作者：
De Voss, JJ;Rutter, K;Barry, CE
通讯作者：
Barry, CE