Intracellular iron accumulation facilitates mycobacterial infection in old mouse macrophages.
Intracellular iron accumulation facilitates mycobacterial infection in old mouse macrophages.
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DOI：
10.1007/s11357-023-01048-1
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发表时间：
2024-04
期刊：
影响因子：
5.6
通讯作者：
Cheng, Yong
中科院分区：
文献类型：
--
作者：
Kotey, Stephen K.;Tan, Xuejuan;Fleming, Owen;Kasiraju, Ramakrishnama Raju;Dagnell, Audrey L.;Van Pelt, Kyle N.;Rogers, Janet;Hartson, Steven D.;Thadathil, Nidheesh;Selvarani, Ramasamy;Ranjit, Rojina;Logan, Sreemathi;Deepa, Sathyaseelan S.;Richardson, Arlan;Cheng, Yong
衰老对免疫系统有重大影响，导致免疫功能逐渐下降，身体对细菌感染的反应能力发生变化。非结核分枝杆菌（NTM），也称为非典型分枝杆菌或环境分枝杆菌，通常存在于土壤、水和各种环境来源中。虽然许多NTM物种被认为是机会性病原体，但有些物种可引起严重感染，特别是在免疫系统受损的个体中，例如老年人。当分枝杆菌进入人体时，巨噬细胞是第一批遇到它们的免疫细胞之一，并试图通过一种称为吞噬作用的过程吞噬分枝杆菌。一些NTM物种，包括鸟分枝杆菌（M. avium）可以在巨噬细胞内存活和复制。然而，对于老年人中NTM和巨噬细胞之间的相互作用知之甚少。在这项研究中，我们研究了从幼龄（5个月）和老年（25个月）小鼠中分离的骨髓源性巨噬细胞（BMMs）对肺NTM疾病患者中主要NTM物种之一的4型鸟分枝杆菌的反应。我们的研究结果表明，与年轻小鼠的bmm相比，老年小鼠的bmm细胞内铁水平增加，更容易感染血清型4型鸟分枝杆菌。全细胞蛋白质组学分析表明，与分枝杆菌感染无关，老年bmm中铁稳态相关蛋白的表达失调。铁螯合剂去铁胺显著地恢复了老年小鼠BMMs中分枝杆菌的杀伤和吞噬溶酶体的成熟。因此，我们的数据首次表明，细胞内铁积累可改善老年小鼠巨噬细胞内NTM的存活，并提示铁螯合药物作为宿主导向治疗老年人肺部NTM感染的潜在应用。在线版本包含补充材料，可在10.1007/s11357-023-01048-1获得。
Aging has a significant impact on the immune system, leading to a gradual decline in immune function and changes in the body’s ability to respond to bacterial infections. Non-tuberculous mycobacteria (NTM), also known as atypical mycobacteria or environmental mycobacteria, are commonly found in soil, water, and various environmental sources. While many NTM species are considered opportunistic pathogens, some can cause significant infections, particularly in individuals with compromised immune systems, such as older individuals. When mycobacteria enter the body, macrophages are among the first immune cells to encounter them and attempt to engulf mycobacteria through a process called phagocytosis. Some NTM species, including Mycobacterium avium (M. avium) can survive and replicate within macrophages. However, little is known about the interaction between NTM and macrophages in older individuals. In this study, we investigated the response of bone marrow–derived macrophage (BMMs) isolated from young (5 months) and old (25 months) mice to M. avium serotype 4, one of the main NTM species in patients with pulmonary NTM diseases. Our results demonstrated that BMMs from old mice have an increased level of intracellular iron and are more susceptible to M. avium serotype 4 infection compared to BMMs from young mice. The whole-cell proteomic analysis indicated a dysregulated expression of iron homeostasis–associated proteins in old BMMs regardless of mycobacterial infection. Deferoxamine, an iron chelator, significantly rescued mycobacterial killing and phagolysosome maturation in BMMs from old mice. Therefore, our data for the first time indicate that an intracellular iron accumulation improves NTM survival within macrophages from old mice and suggest a potential application of iron-chelating drugs as a host-directed therapy for pulmonary NTM infection in older individuals. The online version contains supplementary material available at 10.1007/s11357-023-01048-1.
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影响因子：
7.1
作者：
Kenkhuis B;Somarakis A;de Haan L;Dzyubachyk O;IJsselsteijn ME;de Miranda NFCC;Lelieveldt BPF;Dijkstra J;van Roon-Mom WMC;Höllt T;van der Weerd L
通讯作者：
van der Weerd L
影响因子：
18.2
作者：
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Stout-Delgado HW
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Neyrolles, Olivier
影响因子：
82.9
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通讯作者：
Slavich, George M.
影响因子：
11.8
作者：
Daley, Charles L.;Iaccarino, Jonathan M.;Winthrop, Kevin L.
通讯作者：
Winthrop, Kevin L.