慢性高血糖会损害巨噬细胞对结核分枝杆菌感染的抗微生物功能。

IF 3.3 4区 医学 Q3 IMMUNOLOGY
Immunologic Research Pub Date : 2024-08-01 Epub Date: 2024-02-12 DOI:10.1007/s12026-024-09462-z
Gaurav Kumar Chaubey, Radheshyam Modanwal, Rahul Dilawari, Sharmila Talukdar, Asmita Dhiman, Surbhi Chaudhary, Anil Patidar, Chaaya Iyengar Raje, Manoj Raje
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引用次数: 0

摘要

糖尿病(DM)是结核病(TB)的一个主要风险因素,但糖尿病与结核病之间的内在联系机制仍不明确。巨噬细胞是先天性免疫反应中的关键角色,其吞噬能力在微生物感染时会增强。在感染或发炎时,巨噬细胞还会产生活性氧(ROS)、活性氮(RNS)、促炎细胞因子(IL-1β 和 IL-6)和抗炎细胞因子(IL-10),从而击退入侵的病原体。然而,巨噬细胞在暴露于高血糖时的这些先天防御能力是否强大仍不清楚。在目前的研究中,我们探讨了这些宿主防御分子在结核分枝杆菌(Mtb)感染和脂多糖(LPS)刺激下产生的反应。利用高脂饮食+链脲佐菌素诱导的糖尿病小鼠腹腔巨噬细胞和高血糖 THP-1 衍生巨噬细胞作为模型系统,我们发现 LPS 刺激和 Mtb 感染不能有效刺激暴露于高血糖的细胞产生 ROS、RNS 和促炎细胞因子。相反,却观察到抗炎细胞因子的产生增加。为了证实糖尿病巨噬细胞抗菌活性降低的机制,我们研究了这些受损巨噬细胞的活化状态,发现活化(TLR-4)和分化标志物(CD11b 和 CD11c)的表面表达降低。我们推测,这可能是糖尿病患者更易感染 Mtb 的原因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Chronic hyperglycemia impairs anti-microbial function of macrophages in response to Mycobacterium tuberculosis infection.

Chronic hyperglycemia impairs anti-microbial function of macrophages in response to Mycobacterium tuberculosis infection.

Diabetes mellitus (DM) is a major risk factor for tuberculosis (TB), though the underlying mechanisms linking DM and TB remain ambiguous. Macrophages are a key player in the innate immune response and their phagocytic ability is enhanced in response to microbial infections. Upon infection or inflammation, they also repel invading pathogens by generating; reactive oxygen species (ROS), reactive nitrogen species (RNS), pro-inflammatory cytokines (IL-1β and IL-6), and anti-inflammatory cytokines (IL-10). However, the robustness of these innate defensive capabilities of macrophages when exposed to hyperglycemia remains unclear. In our current work, we explored the production of these host defense molecules in response to challenge with Mycobacterium tuberculosis (Mtb) infection and lipopolysaccharide (LPS) stimulation. Utilizing peritoneal macrophages from high-fat diet + streptozotocin induced diabetic mice and hyperglycemic THP-1-derived macrophages as model systems; we found that LPS stimulation and Mtb infection were ineffective in stimulating the production of ROS, RNS, and pro-inflammatory cytokines in cells exposed to hyperglycemia. On the contrary, an increase in production of anti-inflammatory cytokines was observed. To confirm the mechanism of decreased anti-bacterial activity of the diabetic macrophage, we explored activation status of these compromised macrophages and found decreased surface expression of activation (TLR-4) and differentiation markers (CD11b and CD11c). We postulate that this could be the cause for higher susceptibility for Mtb infection among diabetic individuals.

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来源期刊
Immunologic Research
Immunologic Research 医学-免疫学
CiteScore
6.90
自引率
0.00%
发文量
83
审稿时长
6-12 weeks
期刊介绍: IMMUNOLOGIC RESEARCH represents a unique medium for the presentation, interpretation, and clarification of complex scientific data. Information is presented in the form of interpretive synthesis reviews, original research articles, symposia, editorials, and theoretical essays. The scope of coverage extends to cellular immunology, immunogenetics, molecular and structural immunology, immunoregulation and autoimmunity, immunopathology, tumor immunology, host defense and microbial immunity, including viral immunology, immunohematology, mucosal immunity, complement, transplantation immunology, clinical immunology, neuroimmunology, immunoendocrinology, immunotoxicology, translational immunology, and history of immunology.
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