{"title":"常驻和浸润免疫细胞通过 IL-18R/IFN-γ/ROS 轴在小鼠体内防御长须鲸军团菌的过程中发挥相反的作用。","authors":"","doi":"10.1016/j.mucimm.2024.05.001","DOIUrl":null,"url":null,"abstract":"<div><div>The immune response against <em>Legionella longbeachae</em>, a causative agent of the often-fatal Legionnaires’ pneumonia, is poorly understood. Here, we investigated the specific roles of tissue-resident alveolar macrophages (AMs) and infiltrating phagocytes during infection with this pathogen. AMs were the predominant cell type that internalized bacteria 1 day after infection. A total of 3 and 5 days after infection, AM numbers were greatly reduced, whereas there was an influx of neutrophils and, later, monocyte-derived cells (MCs) into lung tissue. AMs carried greater numbers of viable <em>L. longbeachae</em> than neutrophils and MCs, which correlated with a higher capacity of <em>L. longbeachae</em> to translocate bacterial effector proteins required for bacterial replication into the AM cytosol. Cell ablation experiments demonstrated that AM promoted infection, whereas neutrophils and MC were required for efficient bacterial clearance. Interleukin (IL)-18 was important for interferon-γ production by IL-18R<sup>+</sup> natural killer cells and T cells, which, in turn, stimulated reactive oxygen species–mediated bactericidal activity in neutrophils, resulting in the restriction of <em>L. longbeachae</em> infection. Ciliated bronchiolar epithelial cells also expressed IL-18R but did not play a role in IL-18–mediated <em>L. longbeachae</em> clearance. Our results have identified opposing innate functions of tissue-resident and infiltrating immune cells during <em>L. longbeachae</em> infection that may be manipulated to improve protective responses.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":null,"pages":null},"PeriodicalIF":7.9000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Opposing roles of resident and infiltrating immune cells in the defense against Legionella longbeachae via IL-18R/IFN-γ/ROS axis in mice\",\"authors\":\"\",\"doi\":\"10.1016/j.mucimm.2024.05.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>The immune response against <em>Legionella longbeachae</em>, a causative agent of the often-fatal Legionnaires’ pneumonia, is poorly understood. Here, we investigated the specific roles of tissue-resident alveolar macrophages (AMs) and infiltrating phagocytes during infection with this pathogen. AMs were the predominant cell type that internalized bacteria 1 day after infection. A total of 3 and 5 days after infection, AM numbers were greatly reduced, whereas there was an influx of neutrophils and, later, monocyte-derived cells (MCs) into lung tissue. AMs carried greater numbers of viable <em>L. longbeachae</em> than neutrophils and MCs, which correlated with a higher capacity of <em>L. longbeachae</em> to translocate bacterial effector proteins required for bacterial replication into the AM cytosol. Cell ablation experiments demonstrated that AM promoted infection, whereas neutrophils and MC were required for efficient bacterial clearance. Interleukin (IL)-18 was important for interferon-γ production by IL-18R<sup>+</sup> natural killer cells and T cells, which, in turn, stimulated reactive oxygen species–mediated bactericidal activity in neutrophils, resulting in the restriction of <em>L. longbeachae</em> infection. Ciliated bronchiolar epithelial cells also expressed IL-18R but did not play a role in IL-18–mediated <em>L. longbeachae</em> clearance. Our results have identified opposing innate functions of tissue-resident and infiltrating immune cells during <em>L. longbeachae</em> infection that may be manipulated to improve protective responses.</div></div>\",\"PeriodicalId\":18877,\"journal\":{\"name\":\"Mucosal Immunology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":7.9000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Mucosal Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1933021924000424\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Mucosal Immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1933021924000424","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Opposing roles of resident and infiltrating immune cells in the defense against Legionella longbeachae via IL-18R/IFN-γ/ROS axis in mice
The immune response against Legionella longbeachae, a causative agent of the often-fatal Legionnaires’ pneumonia, is poorly understood. Here, we investigated the specific roles of tissue-resident alveolar macrophages (AMs) and infiltrating phagocytes during infection with this pathogen. AMs were the predominant cell type that internalized bacteria 1 day after infection. A total of 3 and 5 days after infection, AM numbers were greatly reduced, whereas there was an influx of neutrophils and, later, monocyte-derived cells (MCs) into lung tissue. AMs carried greater numbers of viable L. longbeachae than neutrophils and MCs, which correlated with a higher capacity of L. longbeachae to translocate bacterial effector proteins required for bacterial replication into the AM cytosol. Cell ablation experiments demonstrated that AM promoted infection, whereas neutrophils and MC were required for efficient bacterial clearance. Interleukin (IL)-18 was important for interferon-γ production by IL-18R+ natural killer cells and T cells, which, in turn, stimulated reactive oxygen species–mediated bactericidal activity in neutrophils, resulting in the restriction of L. longbeachae infection. Ciliated bronchiolar epithelial cells also expressed IL-18R but did not play a role in IL-18–mediated L. longbeachae clearance. Our results have identified opposing innate functions of tissue-resident and infiltrating immune cells during L. longbeachae infection that may be manipulated to improve protective responses.
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.