长须鲸军团菌对中性粒细胞杀微生物反应的抑制和规避。

IF 5.1 1区 生物学 Q1 MICROBIOLOGY
mBio Pub Date : 2025-02-05 Epub Date: 2024-12-16 DOI:10.1128/mbio.03274-24
Hannah E Hanford, Christopher T D Price, Silvia Uriarte, Yousef Abu Kwaik
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引用次数: 0

摘要

军团菌逃避降解并在肺泡巨噬细胞内增殖,是疾病表现的必要步骤。然而,大多数细胞内细菌病原体被限制在中性粒细胞中,这是先天免疫防御入侵病原体的第一道防线。嗜中性粒细胞内的细菌降解是由杀微生物颗粒与含病原体的吞噬体融合以及吞噬细胞NADPH氧化酶复合物产生活性氧(ROS)介导的。在这里,我们表明人类中性粒细胞不能触发杀微生物过程,因此不能限制长滩乳杆菌。此外,被长滩乳杆菌感染的中性粒细胞不能产生强大的促炎反应,如脱颗粒和IL-8的产生。在这里,我们确定了长滩乳杆菌采用的三种策略来逃避中性粒细胞的限制,并抑制中性粒细胞对同一细胞中共存的其他细菌的杀微生物反应。首先,L. longbeach将吞噬细胞NADPH氧化酶复合物的胞质亚基和膜结合亚基从独立于4型分泌系统(T4SS)的吞噬体膜中排除。因此,受感染的中性粒细胞不能对L. longbeache产生强大的ROS。其次,L. longbeachae通过不依赖t4ss的机制阻碍嗜氮颗粒与自身吞噬体和共存于同一细胞的细菌吞噬体融合。第三,L. longbeache通过反式作用的t4ss依赖机制保护共存细菌的吞噬体不被ROS降解。总之,我们得出结论,L. longbeach通过不依赖t4ss的机制逃避人类中性粒细胞的限制,并利用反式作用的t4ss依赖机制抑制整个细胞质中中性粒细胞ROS的产生。重要性:长滩军团菌通常存在于土壤环境中,它与多种原生宿主和微生物竞争对手相互作用。在传播给人类后,长滩乳杆菌在肺泡巨噬细胞内侵入并复制,导致肺炎的表现。除了肺泡巨噬细胞外,中性粒细胞是丰富的免疫细胞,作为抵御入侵病原体的第一道防线。虽然大多数细胞内细菌物种被中性粒细胞杀死和降解,但我们发现长滩乳杆菌逃避降解。病原体破坏了主要中性粒细胞的杀微生物过程,包括杀微生物颗粒与含病原体液泡的融合。通过抑制吞噬细胞NADPH氧化酶复合物的组装,病原体阻止中性粒细胞产生杀微生物的活性氧。总的来说,长滩乳杆菌采用独特的毒力策略来逃避中性粒细胞的主要杀微生物过程。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Inhibition and evasion of neutrophil microbicidal responses by Legionella longbeachae.

Legionella species evade degradation and proliferate within alveolar macrophages as an essential step for the manifestation of disease. However, most intracellular bacterial pathogens are restricted in neutrophils, which are the first line of innate immune defense against invading pathogens. Bacterial degradation within neutrophils is mediated by the fusion of microbicidal granules to pathogen-containing phagosomes and the generation of reactive oxygen species (ROS) by the phagocyte NADPH oxidase complex. Here, we show that human neutrophils fail to trigger microbicidal processes and, consequently, fail to restrict L. longbeachae. In addition, neutrophils infected with L. longbeachae fail to undergo a robust pro-inflammatory response, such as degranulation and IL-8 production. Here, we identify three strategies employed by L. longbeachae for evading restriction by neutrophils and inhibiting the neutrophil microbicidal response to other bacteria co-inhabiting in the same cell. First, L. longbeachae excludes the cytosolic and membrane-bound subunits of the phagocyte NADPH oxidase complex from its phagosomal membrane independent of the type 4 secretion system (T4SS). Consequently, infected neutrophils fail to generate robust ROS in response to L. longbeachae. Second, L. longbeachae impedes the fusion of azurophilic granules to its phagosome and the phagosomes of bacteria co-inhabiting the same cell through T4SS-independent mechanisms. Third, L. longbeachae protects phagosomes of co-inhabiting bacteria from degradation by ROS through a trans-acting T4SS-dependent mechanism. Collectively, we conclude that L. longbeachae evades restriction by human neutrophils via T4SS-independent mechanisms and utilizes trans-acting T4SS-dependent mechanisms for inhibition of neutrophil ROS generation throughout the cell cytosol.

Importance: Legionella longbeachae is commonly found in soil environments where it interacts with a wide variety of protist hosts and microbial competitors. Upon transmission to humans, L. longbeachae invades and replicates within alveolar macrophages, leading to the manifestation of pneumonia. In addition to alveolar macrophages, neutrophils are abundant immune cells acting as the first line of defense against invading pathogens. While most intracellular bacterial species are killed and degraded by neutrophils, we show that L. longbeachae evades degradation. The pathogen impairs the major neutrophils' microbicidal processes, including the fusion of microbicidal granules to the pathogen-containing vacuole. By inhibiting of assembly of the phagocyte NADPH oxidase complex, the pathogen blocks neutrophils from generating microbicide reactive oxygen species. Overall, L. longbeachae employs unique virulence strategies to evade the major microbicidal processes of neutrophils.

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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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