文章基本信息

标题：Gata2 heterozygous mutant mice exhibit reduced inflammatory responses and impaired bacterial clearance
本地全文：下载
作者：Jun Takai ; Takashi Shimada ; Tadaho Nakamura 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：8
页码：1-19
DOI：10.1016/j.isci.2021.102836
语种：English
出版社：Elsevier
摘要：SummaryInfectious diseases continually pose global medical challenges. The transcription factor GATA2 establishes gene networks and defines cellular identity in hematopoietic stem/progenitor cells and in progeny committed to specific lineages. GATA2-haploinsufficient patients exhibit a spectrum of immunodeficiencies associated with bacterial, viral, and fungal infections. Despite accumulating clinical knowledge of the consequences of GATA2 haploinsufficiency in humans, it is unclear how GATA2 haploinsufficiency compromises host anti-infectious defenses. To address this issue, we examinedGata2-heterozygous mutant (G2Het) mice as a model for human GATA2 haploinsufficiency.In vivoinflammation imaging and cytokine multiplex analysis demonstrated thatG2Hetmice had attenuated inflammatory responses with reduced levels of inflammatory cytokines, particularly IFN-γ, IL-12p40, and IL-17A, during lipopolysaccharide-induced acute inflammation. Consequently, bacterial clearance was significantly impaired inG2Hetmice after cecal ligation and puncture-induced polymicrobial peritonitis. These results provide direct molecular insights into GATA2-directed host defenses and the pathogenic mechanisms underlying observed immunodeficiencies in GATA2-haploinsufficient patients.Graphical abstractDisplay OmittedHighlights•Gata2Hetmice exhibited reduced inflammation than WT mice in response to bacteria•After polymicrobial peritonitis, bacterial clearance was impaired inGata2Hetmice•During inflammation, IFN-γ, IL-12p40, and IL-17A were lower inGata2Hetmice•Inflammation imaging was performed during peritonitis and sepsis inhIL-6Luc miceMolecular biology; Immunology