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干扰素刺激的巨噬细胞通过自噬和释放一氧化氮来限制结核分枝杆菌的生长。

Infergen Stimulated Macrophages Restrict Mycobacterium tuberculosis Growth by Autophagy and Release of Nitric Oxide.

机构信息

Immunology Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, 160036, India.

Department of Biotechnology, Panjab University, Chandigarh, 160014, India.

出版信息

Sci Rep. 2016 Dec 21;6:39492. doi: 10.1038/srep39492.

DOI:10.1038/srep39492
PMID:28000752
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5175149/
Abstract

IFN alfacon-1 (Infergen) is a synthetic form of Interferon (IFN)-α2b. Infergen has immunomodulatory activity and is effective against hepatitis C virus. However, the effect of Infergen (IFG) on Mycobacterium tuberculosis (Mtb) has not yet been reported. Therefore, for the first time, we have studied the influence of IFG in constraining the survival of Mtb in human macrophages. We observed that IFG significantly enhanced the maturation and activation of macrophages. Further, it substantially augmented the secretion of IL-6, nitric oxide (NO) and antigen uptake. Moreover, macrophages exhibited remarkably higher bactericidal activity, as evidenced by reduction in the Mtb growth. Infergen-mediated mechanism was different from the type-1 interferons; since it worked through the activation of NF-κB, phosphorylation of STAT-3 and Akt-PI3K that improved the bactericidal activity through autophagy and NO release. In future, IFG immunotherapy can be a novel strategy for treating patients and controlling TB.

摘要

IFN alfacon-1(Infergen)是一种合成的干扰素(IFN)-α2b。Infergen 具有免疫调节活性,对丙型肝炎病毒有效。然而,Infergen(IFG)对结核分枝杆菌(Mtb)的影响尚未见报道。因此,我们首次研究了 IFG 对限制人巨噬细胞中 Mtb 存活的影响。我们观察到 IFG 显著增强了巨噬细胞的成熟和激活。此外,它还大大增加了白细胞介素 6(IL-6)、一氧化氮(NO)和抗原摄取的分泌。此外,巨噬细胞表现出更高的杀菌活性,这表明 Mtb 的生长减少。IFG 介导的机制与 1 型干扰素不同;因为它通过 NF-κB 的激活、STAT-3 的磷酸化和 Akt-PI3K 的磷酸化起作用,通过自噬和 NO 释放提高杀菌活性。将来,IFG 免疫疗法可以成为治疗患者和控制结核病的一种新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/017d/5175149/a5c67fdbeb5e/srep39492-f7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/017d/5175149/f7124a04c167/srep39492-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/017d/5175149/b134d28b3062/srep39492-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/017d/5175149/a5c67fdbeb5e/srep39492-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/017d/5175149/a2c9a057618a/srep39492-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/017d/5175149/620b0554e11d/srep39492-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/017d/5175149/4c811160939b/srep39492-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/017d/5175149/2224827033fb/srep39492-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/017d/5175149/f7124a04c167/srep39492-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/017d/5175149/b134d28b3062/srep39492-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/017d/5175149/a5c67fdbeb5e/srep39492-f7.jpg

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