Impact of nicotine and cotinine on macrophage inflammatory plasticity via vesicular modifications in gastrointestinal bacteria

IF 2.6 3区生物学 Q3 MICROBIOLOGY Anaerobe Pub Date : 2023-10-01 DOI:10.1016/j.anaerobe.2023.102787

Jourdan E. Lakes , Xu Fu , Brock T Harvey , Khaga R. Neupane , Surya P. Aryal , Jessica L. Ferrell , Michael D. Flythe , Christopher I. Richards

{"title":"Impact of nicotine and cotinine on macrophage inflammatory plasticity via vesicular modifications in gastrointestinal bacteria","authors":"Jourdan E. Lakes , Xu Fu , Brock T Harvey , Khaga R. Neupane , Surya P. Aryal , Jessica L. Ferrell , Michael D. Flythe , Christopher I. Richards","doi":"10.1016/j.anaerobe.2023.102787","DOIUrl":null,"url":null,"abstract":"<div><h3>Objectives</h3><p><span>This study aimed to elucidate mechanistic explanation(s) for compositional changes to enteric microflora by determining the impacts of continuous nicotine/cotinine exposure on representative gastrointestinal bacteria and how these alterations impact innate </span>immune cell plasticity.</p></div><div><h3>Methods</h3><p><em>In vitro</em> cultures of the gastrointestinal bacteria (<span><em>Bacteroides fragilis</em></span> 25285, <span><em>Prevotella</em><em> bryantii</em></span> B<sub>1</sub>4, and <em>Acetoanaerobium sticklandii</em><span><span> SR) were continuously exposed to nicotine or cotinine. Supernatant samples were collected for fermentation acid analysis. Vesicles were collected and analyzed for physiological changes in number, size, and total protein cargo. Cultured macrophages were stimulated to a tolerogenic phenotype, exposed to control or altered (nicotine or cotinine – exposed) vesicles, and inflammatory plasticity assessed via inflammatory </span>cytokine production.</span></p></div><div><h3>Results</h3><p><span>Nicotine/cotinine exposure differentially affected metabolism of all bacteria tested in a Gram (nicotine) and concentration-dependent (cotinine) manner. Physiological studies demonstrated changes in vesiculation number and protein cargo following nicotine/cotinine exposures. Continuous exposure to 1 μM nicotine and 10 μM cotinine concentrations reduced total protein cargo of Gram (-) – 25285 and B</span><sub>1</sub>4 vesicles, while cotinine generally increased total protein in Gram (+) - SR vesicles. We found that theses physiological changes to the vesicles of 25285 and SR formed under nicotine and cotinine, respectively, challenged the plasticity of tolerogenic macrophages. Tolerogenic macrophages exposed to vesicles from 1 μM nicotine, and 5 or 10 μΜ cotinine cultures produced significantly less IL-12p70, TNFα, or KC/GRO, regardless of macrophage exposure to nicotine/cotinine.</p></div><div><h3>Conclusions</h3><p>Nicotine/cotinine exposure differentially alters bacterial metabolism and vesicle physiology, ultimately impacting the inflammatory response of tolerogenic macrophages.</p></div>","PeriodicalId":8050,"journal":{"name":"Anaerobe","volume":"83 ","pages":"Article 102787"},"PeriodicalIF":2.6000,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Anaerobe","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1075996423000963","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MICROBIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Objectives

This study aimed to elucidate mechanistic explanation(s) for compositional changes to enteric microflora by determining the impacts of continuous nicotine/cotinine exposure on representative gastrointestinal bacteria and how these alterations impact innate immune cell plasticity.

Methods

In vitro cultures of the gastrointestinal bacteria (Bacteroides fragilis 25285, Prevotella bryantii B₁4, and Acetoanaerobium sticklandii SR) were continuously exposed to nicotine or cotinine. Supernatant samples were collected for fermentation acid analysis. Vesicles were collected and analyzed for physiological changes in number, size, and total protein cargo. Cultured macrophages were stimulated to a tolerogenic phenotype, exposed to control or altered (nicotine or cotinine – exposed) vesicles, and inflammatory plasticity assessed via inflammatory cytokine production.

Results

Nicotine/cotinine exposure differentially affected metabolism of all bacteria tested in a Gram (nicotine) and concentration-dependent (cotinine) manner. Physiological studies demonstrated changes in vesiculation number and protein cargo following nicotine/cotinine exposures. Continuous exposure to 1 μM nicotine and 10 μM cotinine concentrations reduced total protein cargo of Gram (-) – 25285 and B₁4 vesicles, while cotinine generally increased total protein in Gram (+) - SR vesicles. We found that theses physiological changes to the vesicles of 25285 and SR formed under nicotine and cotinine, respectively, challenged the plasticity of tolerogenic macrophages. Tolerogenic macrophages exposed to vesicles from 1 μM nicotine, and 5 or 10 μΜ cotinine cultures produced significantly less IL-12p70, TNFα, or KC/GRO, regardless of macrophage exposure to nicotine/cotinine.

Conclusions

Nicotine/cotinine exposure differentially alters bacterial metabolism and vesicle physiology, ultimately impacting the inflammatory response of tolerogenic macrophages.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

尼古丁和可替宁通过胃肠道细菌的囊泡修饰对巨噬细胞炎症可塑性的影响。

目的：本研究旨在通过确定持续暴露于尼古丁/可替宁对代表性胃肠道细菌的影响，以及这些变化如何影响先天免疫细胞的可塑性，来阐明肠道菌群组成变化的机制解释。方法：将胃肠道细菌（脆弱拟杆菌25285、bryantii Prevotella B14和粘性丙酮厌氧菌SR）的体外培养物连续暴露于尼古丁或可替宁。收集上清液样品用于发酵酸分析。收集囊泡并分析其数量、大小和总蛋白质含量的生理变化。培养的巨噬细胞被刺激至耐受表型，暴露于对照或改变（尼古丁或可替宁暴露）的囊泡，并通过炎症细胞因子的产生评估炎症可塑性。结果：尼古丁/可替宁暴露以革兰氏（尼古丁）和浓度依赖性（可替宁）方式对所有受试细菌的代谢产生不同影响。生理学研究表明，尼古丁/可替宁暴露后膀胱数和蛋白质含量发生变化。持续暴露于1 μM尼古丁和10 μM可替宁浓度降低了Gram（-）-25285和B14囊泡的总蛋白载量，而可替宁通常增加了Gram+SR囊泡中的总蛋白。我们发现，在尼古丁和可替宁作用下分别形成的25285和SR囊泡的这些生理变化挑战了耐受性巨噬细胞的可塑性。暴露于1μM尼古丁囊泡和5或10μΜ可替宁培养物的Tolerogenic巨噬细胞产生的IL-12p70、TNFα或KC/GRO显著减少，无论巨噬细胞暴露于尼古丁/可替宁。结论：尼古丁/可替宁暴露不同程度地改变细菌代谢和囊泡生理，最终影响致耐受巨噬细胞的炎症反应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Anaerobe 生物-微生物学

CiteScore

5.20

自引率

8.70%

发文量

137

审稿时长

76 days

期刊介绍： Anaerobe is essential reading for those who wish to remain at the forefront of discoveries relating to life processes of strictly anaerobes. The journal is multi-disciplinary, and provides a unique forum for those investigating anaerobic organisms that cause infections in humans and animals, as well as anaerobes that play roles in microbiomes or environmental processes. Anaerobe publishes reviews, mini reviews, original research articles, notes and case reports. Relevant topics fall into the broad categories of anaerobes in human and animal diseases, anaerobes in the microbiome, anaerobes in the environment, diagnosis of anaerobes in clinical microbiology laboratories, molecular biology, genetics, pathogenesis, toxins and antibiotic susceptibility of anaerobic bacteria.