Intravacuolar persistence in neutrophils facilitates Listeria monocytogenes spread to co-cultured cells.

IF 5.1 1区 生物学 Q1 MICROBIOLOGY
mBio Pub Date : 2025-04-09 Epub Date: 2025-03-11 DOI:10.1128/mbio.02700-24
Stefano Bagatella, Camille Monney, Natascha Gross, Véronique Bernier Gosselin, Gertraud Schüpbach-Regula, Andrew Hemphill, Anna Oevermann
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引用次数: 0

Abstract

The bacterium Listeria monocytogenes (Lm) causes listeriosis in humans and ruminants. Acute lesions are predominantly infiltrated by polymorphonuclear neutrophils (PMNs), considered to be the efficient bactericidal arm of innate immunity. However, recent evidence suggests that PMNs cannot achieve antilisterial sterilizing immunity and that Lm may persist within PMNs. Despite this, interactions between PMNs and Lm remain poorly understood. In this study, we characterized the listericidal activity and interaction dynamics of bovine PMNs with Lm ex vivo. Phagocytosed Lm failed to escape into the PMN cytosol and was primarily targeted by phagolysosomal mechanisms. However, PMNs enabled prolonged intravacuolar survival of a resilient Lm subpopulation, largely as viable but non-culturable (VBNC) bacteria. This resilient Lm population could spread from PMNs to a cell line, resuscitate, and complete its canonical life cycle, thereby perpetuating the infection. Therefore, we identify PMNs as a mobile niche for Lm survival and provide evidence that PMNs harbor VBNC bacteria, potentially facilitating Lm dissemination within the host.

Importance: Listeria monocytogenes (Lm) is a significant foodborne pathogen responsible for high hospitalization rates in humans, especially vulnerable groups such as the elderly, pregnant women, and immunocompromised individuals. In animals like ruminants, Lm infection leads to severe disease manifestations, notably brainstem encephalitis. This study uncovers a novel mechanism by which bovine neutrophils (PMNs) harbor Lm in a viable but non-culturable (VBNC) state, enabling the bacteria to hide in the host. PMNs, traditionally viewed as bacteria killers, may serve as Trojan horses, allowing Lm to persist and spread within the host. This discovery has broad implications for understanding Lm's persistence, its role in recurrent infections, and the development of new therapeutic strategies targeting VBNC forms of Lm to improve treatment outcomes and disease control.

嗜中性粒细胞的胞浆内持久性有助于李斯特菌向共培养细胞扩散。
单核增生李斯特菌(Lm)在人类和反刍动物中引起李斯特菌病。急性病变主要由多形核中性粒细胞(pmn)浸润,被认为是先天免疫的有效杀菌臂。然而,最近的证据表明pmn不能实现抗李斯特菌杀菌免疫,并且Lm可能在pmn中持续存在。尽管如此,pmn和Lm之间的相互作用仍然知之甚少。在本研究中,我们研究了牛PMNs与Lm的体外杀菌活性和相互作用动力学。被吞噬的Lm不能逃逸到PMN细胞质中,主要是被吞噬溶酶体机制靶向。然而,PMNs能够延长弹性Lm亚群的孔内存活时间,主要是作为可存活但不可培养的(VBNC)细菌。这种有弹性的Lm种群可以从pmn传播到细胞系,复苏并完成其规范的生命周期,从而使感染永久化。因此,我们将pmn确定为Lm存活的移动生态位,并提供证据表明pmn含有VBNC细菌,可能促进Lm在宿主内的传播。重要性:单核细胞增生李斯特菌(Lm)是一种重要的食源性病原体,导致人类住院率高,尤其是老年人、孕妇和免疫功能低下个体等弱势群体。在反刍动物等动物中,Lm感染会导致严重的疾病表现,特别是脑干脑炎。本研究揭示了牛中性粒细胞(PMNs)在活但不可培养(VBNC)状态下携带Lm的新机制,使细菌能够隐藏在宿主体内。传统上被视为细菌杀手的pmn可能充当特洛伊木马,使Lm在宿主体内持续存在和传播。这一发现对于理解Lm的持久性、其在复发性感染中的作用,以及开发针对VBNC形式Lm的新治疗策略以改善治疗效果和疾病控制具有广泛意义。
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
mBio
mBio MICROBIOLOGY-
CiteScore
10.50
自引率
3.10%
发文量
762
审稿时长
1 months
期刊介绍: mBio® is ASM''s first broad-scope, online-only, open access journal. mBio offers streamlined review and publication of the best research in microbiology and allied fields.
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