Quantitative Lipid Droplet Proteomics Reveals Mycobacterium tuberculosis Induced Alterations in Macrophage Response to Infection.,ACS Infectious Diseases

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Quantitative Lipid Droplet Proteomics Reveals Mycobacterium tuberculosis Induced Alterations in Macrophage Response to Infection.
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2019-02-04 , DOI: 10.1021/acsinfecdis.8b00301
Dilip Menon _{1,

2} , Kaurab Singh _{1,

2} , Sneha M Pinto ₃ , Ananya Nandy _{1,

2} , Neetika Jaisinghani _{1,

2} , Rintu Kutum _{2,

4} , Debasis Dash _{2,

4} , T S Keshava Prasad _{3,

5} , Sheetal Gandotra _{1,

2}

Affiliation

Growing evidence suggests the importance of lipid metabolism in pathogenesis of tuberculosis. Neutral lipids form the majority of lipids in a caseous granuloma, a pathology characteristic of tuberculosis. Cytosolic lipid droplets (LDs) of macrophages form the store house of these lipids and have been demonstrated to contribute to the inflammatory response to infection. The proteome of lipid droplets reflects the mechanisms of lipid metabolism active under a condition. However, infection induced changes in the proteome of these dynamic organelles remains elusive. Here, we employed quantitative proteomics to identify alterations induced upon infection with live Mycobacterium tuberculosis (Mtb) in comparison with heat killed bacilli or uninfected macrophages. We found increased abundance of proteins coupled with lipid metabolism, protein synthesis, and vesicular transport function in LDs upon infection with live Mtb. Using biochemical methods and microscopy, we validated ADP-ribosyltransferase (Arf)-like 8 (ARL8B) to be increased on the lipid droplet surface of live Mtb infected macrophages and that ARL8B is a bonafide LD protein. This study provides the first proteomic evidence that the dynamic responses to infection also encompass changes at the level of LDs. This information will be important in understanding how Mtb manipulates lipid metabolism and defense mechanisms of the host macrophage.

中文翻译：

定量脂滴蛋白质组学揭示了结核分枝杆菌诱导的巨噬细胞对感染反应的改变。

越来越多的证据表明脂质代谢在结核病发病机制中的重要性。中性脂质形成干酪样肉芽肿中的大部分脂质，这是结核病的病理学特征。巨噬细胞的细胞溶质脂滴 (LD) 形成这些脂质的储藏室，并已被证明有助于对感染的炎症反应。脂滴的蛋白质组反映了在一定条件下脂质代谢活跃的机制。然而，感染引起的这些动态细胞器蛋白质组的变化仍然难以捉摸。在这里，我们采用定量蛋白质组学来鉴定与热灭活杆菌或未感染巨噬细胞相比，感染活结核分枝杆菌 (Mtb) 后诱导的变化。我们发现与脂质代谢、蛋白质合成、感染活 Mtb 后 LDs 中的囊泡运输功能。使用生化方法和显微镜，我们验证了 ADP-核糖基转移酶 (Arf) 样 8 (ARL8B) 在活 Mtb 感染的巨噬细胞的脂滴表面上增加，并且 ARL8B 是一种真正的 LD 蛋白。这项研究提供了第一个蛋白质组学证据，表明对感染的动态反应也包括 LD 水平的变化。这些信息对于了解 Mtb 如何操纵宿主巨噬细胞的脂质代谢和防御机制非常重要。这项研究提供了第一个蛋白质组学证据，表明对感染的动态反应也包括 LD 水平的变化。这些信息对于了解 Mtb 如何操纵宿主巨噬细胞的脂质代谢和防御机制非常重要。这项研究提供了第一个蛋白质组学证据，表明对感染的动态反应也包括 LD 水平的变化。这些信息对于了解 Mtb 如何操纵宿主巨噬细胞的脂质代谢和防御机制非常重要。

更新日期：2019-01-21

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