Michelle Sue Jann Lee, Julia Matsuo-Dapaah, Camila Del Rosario Zorrilla, Yoshiki Omatsu, Takashi Nagasawa, Shun Uemura, Atsushi Iwama, Ken J Ishii, Cevayir Coban
{"title":"Acute malaria suppresses the B lymphocytic niche in the bone marrow through the alteration of CXCL12-abundant reticular cells.","authors":"Michelle Sue Jann Lee, Julia Matsuo-Dapaah, Camila Del Rosario Zorrilla, Yoshiki Omatsu, Takashi Nagasawa, Shun Uemura, Atsushi Iwama, Ken J Ishii, Cevayir Coban","doi":"10.1093/intimm/dxae012","DOIUrl":null,"url":null,"abstract":"<p><p>Bone marrow is a dynamic organ composed of stem cells that constantly receive signals from stromal cells and other hematopoietic cells in the niches of the bone marrow to maintain hematopoiesis and generate immune cells. Perturbation of the bone marrow microenvironment by infection and inflammation affects hematopoiesis and may affect immune cell development. Little is known about the effect of malaria on the bone marrow stromal cells that govern the hematopoietic stem cell (HSC) niche. In this study, we demonstrate that the mesenchymal stromal CXCL12-abundant reticular (CAR) cell population is reduced during acute malaria infection. The reduction of CXCL12 and interleukin-7 signals in the bone marrow impairs the lymphopoietic niche, leading to the depletion of common lymphoid progenitors, B cell progenitors, and mature B cells, including plasma cells in the bone marrow. We found that interferon-γ (IFNγ) is responsible for the upregulation of Sca1 on CAR cells, yet the decline in CAR cell and B cell populations in the bone marrow is IFNγ-independent. In contrast to the decline in B cell populations, HSCs and multipotent progenitors increased with the expansion of myelopoiesis and erythropoiesis, indicating a bias in the differentiation of multipotent progenitors during malaria infection. These findings suggest that malaria may affect host immunity by modulating the bone marrow niche.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11161414/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/intimm/dxae012","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Bone marrow is a dynamic organ composed of stem cells that constantly receive signals from stromal cells and other hematopoietic cells in the niches of the bone marrow to maintain hematopoiesis and generate immune cells. Perturbation of the bone marrow microenvironment by infection and inflammation affects hematopoiesis and may affect immune cell development. Little is known about the effect of malaria on the bone marrow stromal cells that govern the hematopoietic stem cell (HSC) niche. In this study, we demonstrate that the mesenchymal stromal CXCL12-abundant reticular (CAR) cell population is reduced during acute malaria infection. The reduction of CXCL12 and interleukin-7 signals in the bone marrow impairs the lymphopoietic niche, leading to the depletion of common lymphoid progenitors, B cell progenitors, and mature B cells, including plasma cells in the bone marrow. We found that interferon-γ (IFNγ) is responsible for the upregulation of Sca1 on CAR cells, yet the decline in CAR cell and B cell populations in the bone marrow is IFNγ-independent. In contrast to the decline in B cell populations, HSCs and multipotent progenitors increased with the expansion of myelopoiesis and erythropoiesis, indicating a bias in the differentiation of multipotent progenitors during malaria infection. These findings suggest that malaria may affect host immunity by modulating the bone marrow niche.
骨髓是一个由干细胞组成的动态器官,干细胞不断接收来自骨髓壁龛中基质细胞和其他造血细胞的信号,以维持造血和生成免疫细胞。感染和炎症对骨髓微环境的干扰会影响造血功能,并可能影响免疫细胞的发育。人们对疟疾对管理造血干细胞(HSC)生态位的骨髓基质细胞的影响知之甚少。在这项研究中,我们证明在急性疟疾感染期间,间质基质CXCL12-丰富网状(CAR)细胞群减少。骨髓中 CXCL12 和 IL-7 信号的减少损害了淋巴造血生态位,导致骨髓中普通淋巴祖细胞、B 细胞祖细胞和成熟 B 细胞(包括浆细胞)的耗竭。我们发现,IFNγ 是导致 CAR 细胞上调 Sca1 的原因,但骨髓中 CAR 细胞和 B 细胞数量的减少与 IFNγ 无关。与 B 细胞数量下降相反,造血干细胞和多能祖细胞随着骨髓造血和红细胞生成的扩大而增加,这表明在疟疾感染期间多能祖细胞的分化出现了偏差。这些研究结果表明,疟疾可能通过调节骨髓生态位来影响宿主的免疫力。
期刊介绍:
International Immunology is an online only (from Jan 2018) journal that publishes basic research and clinical studies from all areas of immunology and includes research conducted in laboratories throughout the world.