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嗜酸性粒细胞作为细菌免疫调节和持续存在的驱动因素。

Eosinophils as drivers of bacterial immunomodulation and persistence.

机构信息

Department of Microbiology and Immunology, Louisiana State University Health Sciences Center at Shreveport, Shreveport, Louisiana, USA.

出版信息

Infect Immun. 2024 Sep 10;92(9):e0017524. doi: 10.1128/iai.00175-24. Epub 2024 Jul 15.

DOI:10.1128/iai.00175-24
PMID:39007622
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11385729/
Abstract

Traditionally, eosinophils have been linked to parasitic infections and pathological disease states. However, emerging literature has unveiled a more nuanced and intricate role for these cells, demonstrating their key functions in maintaining mucosal homeostasis. Eosinophils exhibit diverse phenotypes and exert multifaceted effects during infections, ranging from promoting pathogen persistence to triggering allergic reactions. Our investigations primarily focus on spp., with particular emphasis on , a natural murine pathogen that induces diseases in mice akin to pertussis in humans. Recent findings from our published work have unveiled a striking interaction between and eosinophils, facilitated by the -mediated mechanism. This interaction serves to enhance pathogen persistence while concurrently delaying adaptive immune responses. Notably, this role of eosinophils is only noted in the absence of a functional signaling pathway, indicating that wild-type , and possibly other spp., possess such adeptness in manipulating eosinophils that the true function of these cells remains obscured during infection. In this review, we present the mounting evidence pointing toward eosinophils as targets of bacterial exploitation, facilitating pathogen persistence and fostering chronic infections in diverse mucosal sites, including the lungs, gut, and skin. We underscore the pivotal role of the master regulator of pathogenesis, the sigma factor BtrS, in orchestrating eosinophil-dependent immunomodulation within the context of pulmonary infection. These putative convergent strategies of targeting eosinophils offer promising avenues for the development of novel therapeutics targeting respiratory and other mucosal pathogens.

摘要

传统上,嗜酸性粒细胞与寄生虫感染和病理性疾病状态有关。然而,新出现的文献揭示了这些细胞更细致和复杂的作用,表明它们在维持黏膜稳态方面的关键功能。嗜酸性粒细胞表现出多种表型,并在感染过程中发挥多方面的作用,从促进病原体持续存在到引发过敏反应。我们的研究主要集中在 spp. 上,特别是 ,一种天然的鼠病原体,在小鼠中引起类似于人类百日咳的疾病。我们已发表的工作中的最新发现揭示了 与嗜酸性粒细胞之间惊人的相互作用,这是由 -介导的机制促成的。这种相互作用有助于增强病原体的持续存在,同时延迟适应性免疫反应。值得注意的是,这种嗜酸性粒细胞的作用仅在功能性 信号通路缺失的情况下才会出现,这表明野生型 ,可能还有其他 spp.,具有如此娴熟地操纵嗜酸性粒细胞的能力,以至于在感染过程中,这些细胞的真正功能仍然被掩盖。在这篇综述中,我们提出了越来越多的证据,表明嗜酸性粒细胞是细菌利用的目标,促进病原体的持续存在,并在包括肺部、肠道和皮肤在内的各种黏膜部位引发慢性感染。我们强调了 发病机制的主要调节因子 BtrS 西格玛因子在协调肺部感染中嗜酸性粒细胞依赖性免疫调节中的关键作用。这些针对嗜酸性粒细胞的假定趋同策略为开发针对呼吸道和其他黏膜病原体的新型治疗方法提供了有前途的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5951/11385729/736902fb7c28/iai.00175-24.f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5951/11385729/00c75a4056b2/iai.00175-24.f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5951/11385729/346c002bc9df/iai.00175-24.f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5951/11385729/736902fb7c28/iai.00175-24.f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5951/11385729/00c75a4056b2/iai.00175-24.f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5951/11385729/346c002bc9df/iai.00175-24.f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5951/11385729/736902fb7c28/iai.00175-24.f003.jpg

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