Translocating bacteria in SIV infection are not stochastic and preferentially express cytosine methyltransferases

IF 7.9 2区 医学 Q1 IMMUNOLOGY
Jacob K. Flynn , Alexandra M. Ortiz , Ivan Vujkovic-Cvijin , Hugh C. Welles , Jennifer Simpson , Fabiola M. Castello Casta , Debra S. Yee , Andrew R. Rahmberg , Kelsie L. Brooks , Marlon De Leon , Samantha Knodel , Kenzie Birse , Laura Noel-Romas , Anshu Deewan , Yasmine Belkaid , Adam Burgener , Jason M. Brenchley
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引用次数: 0

Abstract

Microbial translocation is a significant contributor to chronic inflammation in people living with HIV (PLWH) and is associated with increased mortality and morbidity in individuals treated for long periods with antiretrovirals. The use of therapeutics to treat microbial translocation has yielded mixed effects, in part, because the species and mechanisms contributing to translocation in HIV remain incompletely characterized. To characterize translocating bacteria, we cultured translocators from chronically SIV-infected rhesus macaques. Proteomic profiling of these bacteria identified cytosine-specific methyltransferases as a common feature and therefore, a potential driver of translocation. Treatment of translocating bacteria with the cytosine methyltransferase inhibitor decitabine significantly impaired growth for several species in vitro. In rhesus macaques, oral treatment with decitabine led to some transient decreases in translocator taxa in the gut microbiome. These data provide mechanistic insight into bacterial translocation in lentiviral infection and explore a novel therapeutic intervention that may improve the prognosis of PLWH.
SIV 感染中的转运细菌并非随机,而是优先表达胞嘧啶甲基转移酶。
微生物易位是导致艾滋病病毒感染者(PLWH)慢性炎症的一个重要因素,并与长期接受抗逆转录病毒药物治疗者的死亡率和发病率增加有关。使用治疗药物治疗微生物易位的效果不一,部分原因是导致艾滋病病毒易位的菌种和机制尚未完全定性。为了确定转运细菌的特征,我们从长期感染 SIV 的猕猴身上培养出了转运细菌。对这些细菌的蛋白质组分析发现,胞嘧啶特异性甲基转移酶是它们的共同特征,因此也是易位的潜在驱动因素。用胞嘧啶甲基转移酶抑制剂地西他滨处理易位细菌,可显著抑制几种细菌在体外的生长。在猕猴体内,地西他滨口服治疗会导致肠道微生物群中的易位分类群短暂减少。这些数据提供了慢病毒感染中细菌易位的机理,并探索了一种可能改善 PLWH 预后的新型治疗干预方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Mucosal Immunology
Mucosal Immunology 医学-免疫学
CiteScore
16.60
自引率
3.80%
发文量
100
审稿时长
12 days
期刊介绍: Mucosal Immunology, the official publication of the Society of Mucosal Immunology (SMI), serves as a forum for both basic and clinical scientists to discuss immunity and inflammation involving mucosal tissues. It covers gastrointestinal, pulmonary, nasopharyngeal, oral, ocular, and genitourinary immunology through original research articles, scholarly reviews, commentaries, editorials, and letters. The journal gives equal consideration to basic, translational, and clinical studies and also serves as a primary communication channel for the SMI governing board and its members, featuring society news, meeting announcements, policy discussions, and job/training opportunities advertisements.
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