Targeted labeling and depletion of alveolar macrophages using VeDTR mouse technology

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-02-09 DOI:10.1016/j.isci.2025.111975

Yuki Nakayama , Miwa Sasai , Ayumi Kuratani , Masaaki Okamoto , Daisuke Okuzaki , Kentaro Yamamoto , Chikako Ono , Masaya Yamaguchi , Shigetada Kawabata , Noriko Shinjyo , Yasutaka Okabe , Yoshiharu Matsuura , Manabu Ato , Masahiro Yamamoto

{"title":"Targeted labeling and depletion of alveolar macrophages using VeDTR mouse technology","authors":"Yuki Nakayama , Miwa Sasai , Ayumi Kuratani , Masaaki Okamoto , Daisuke Okuzaki , Kentaro Yamamoto , Chikako Ono , Masaya Yamaguchi , Shigetada Kawabata , Noriko Shinjyo , Yasutaka Okabe , Yoshiharu Matsuura , Manabu Ato , Masahiro Yamamoto","doi":"10.1016/j.isci.2025.111975","DOIUrl":null,"url":null,"abstract":"<div><div>Alveolar macrophages (AMs) are essential for maintaining lung homeostasis. However, their roles in respiratory infections have been controversial because the methods of depleting them have often suffered from poor cell selectivity. To resolve this problem, we here used VeDTR technology to generate a transgenic mouse line in which AMs can be specifically depleted using diphtheria toxin. When various respiratory infections were examined using this system, we found that AMs prevented the proliferation of <em>Mycobacterium abscessus</em>. This result differed from previous findings using clodronate liposomes to deplete macrophages. We also revealed that the disappearance of AMs contributes to the reduction of bacterial load in the lungs and that AMs are indispensable for GM-CSF-mediated defense against <em>M. abscessus</em> infection. Taken together, the development of an AM-specific depletion system has provided an opportunity to study the roles of AMs in various respiratory infections from a different perspective.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111975"},"PeriodicalIF":4.6000,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"iScience","FirstCategoryId":"103","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2589004225002354","RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Alveolar macrophages (AMs) are essential for maintaining lung homeostasis. However, their roles in respiratory infections have been controversial because the methods of depleting them have often suffered from poor cell selectivity. To resolve this problem, we here used VeDTR technology to generate a transgenic mouse line in which AMs can be specifically depleted using diphtheria toxin. When various respiratory infections were examined using this system, we found that AMs prevented the proliferation of Mycobacterium abscessus. This result differed from previous findings using clodronate liposomes to deplete macrophages. We also revealed that the disappearance of AMs contributes to the reduction of bacterial load in the lungs and that AMs are indispensable for GM-CSF-mediated defense against M. abscessus infection. Taken together, the development of an AM-specific depletion system has provided an opportunity to study the roles of AMs in various respiratory infections from a different perspective.

Abstract Image

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

期刊介绍： Science has many big remaining questions. To address them, we will need to work collaboratively and across disciplines. The goal of iScience is to help fuel that type of interdisciplinary thinking. iScience is a new open-access journal from Cell Press that provides a platform for original research in the life, physical, and earth sciences. The primary criterion for publication in iScience is a significant contribution to a relevant field combined with robust results and underlying methodology. The advances appearing in iScience include both fundamental and applied investigations across this interdisciplinary range of topic areas. To support transparency in scientific investigation, we are happy to consider replication studies and papers that describe negative results. We know you want your work to be published quickly and to be widely visible within your community and beyond. With the strong international reputation of Cell Press behind it, publication in iScience will help your work garner the attention and recognition it merits. Like all Cell Press journals, iScience prioritizes rapid publication. Our editorial team pays special attention to high-quality author service and to efficient, clear-cut decisions based on the information available within the manuscript. iScience taps into the expertise across Cell Press journals and selected partners to inform our editorial decisions and help publish your science in a timely and seamless way.