TAK1 Deficiency in Macrophages Increases Host Susceptibility to Leishmania Infection  

作　　者：Xiankai Cao Kossiwa C.Kokou Shi Yu Mengdan Chen Junling Niu HervéLecoeur Eric Prina Gerald F.Späth Guangxun Meng 

机构地区：[1]The Center for Microbes,Development and Health,CAS Key Laboratory of Molecular Virology&Immunology,University of Chinese Academy of Sciences,Shanghai,China [2]Institute Pasteur,Paris City University,INSERM U1201,Molecular Parasitology and Signalling Unit,Paris,France [3]Pasteurien College,Soochow University,Suzhou,China [4]Nanjing Advanced Academy of Life and Health,Nanjing,China.

出　　处：《Infectious Microbes & Diseases》2023年第3期127-136,共10页感染微生物与疾病（英文）

基　　金：supported by grants from the Institute Pasteur International Direction,International Partnership Program(153831KYSB20190008);the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29030303);the National Key Basic Research Program(2018YFA0507300,2022YFC2304700,2022YFC2303200);the National Natural Science Foundation of China(81830049,92269202);the Shanghai Municipal Science and Technology Major Project(#2019SHZDZX02);the Research Leader Program(#20XD1403900);the Innovation Capacity Building Project of Jiangsu province(BM2020019)。

摘　　要：Leishmania parasites mainly infect macrophages and may cause severe immunopathologies in their host,which are called leishman-iases.In the current work,we infected human and mouse macrophages in vitro with Leishmania major,an etiological agent of cu-taneous leishmaniasis,and found that inhibition or deletion of the transforming growth factorβ–activated kinase 1(TAK1)gene re-sulted in increased parasite loads.In vivo,following a challenge with L.major,mice with a macrophage-specific deletion of TAK1 showed increased clinical signs and higher parasite loads compared with wild-type controls.TAK1 deficiency in mouse macro-phages led to biased Th2 cell responses during the acute stage of infection,characterized by a decrease in interferon-γexpression,and increased expression of IL-4,IL-5 and IL-10.Finally,we found that,in the late stage of L.major infection,excessive Th2-related cytokines led to high arginase 1 expression in mouse tissues and a significant reduction of NO production both locally and system-ically,resulting in compromised control of Leishmania.These findings suggest that TAK1 plays a vital role in host resistance to Leish-mania infection.

关 键 词：TAK1 MACROPHAGE Leishmania major arginase 1 nitric oxide 

分 类 号：R392[医药卫生—免疫学]