The Toxoplasma effector GRA28 promotes parasite dissemination by inducing dendritic cell-like migratory properties in infected macrophages

被引：22

作者：

Ten Hoeve, Arne L. ^{[1
]}

Braun, Laurence ^{[2
]}

Rodriguez, Matias E. ^{[1
]}

Olivera, Gabriela C. ^{[1
]}

Bougdour, Alexandre ^{[2
]}

Belmudes, Lucid ^{[3
]}

Coute, Yohann ^{[3
]}

Saeij, Jeroen P. J. ^{[4
]}

Hakimi, Mohamed-Ali ^{[2
]}

Barragan, Antonio ^{[1
]}

机构：

[1] Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, S-10691 Stockholm, Sweden

[2] Univ Grenoble Alpes, Inst Adv Biosci, CNRS UMR5309, INSERM U1209, Grenoble, France

[3] Univ Grenoble Alpes, INSERM, CEA,FR2048, UMR BioSante U1292,CNRS, F-38000 Grenoble, France

[4] Univ Calif Davis, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA

来源：

CELL HOST & MICROBE | 2022年 / 30卷 / 09期

基金：

瑞典研究理事会;

关键词：

DENSE GRANULE PROTEIN; ORAL INFECTION; GONDII INFECTION; IMMUNE-RESPONSE; HOST-RESISTANCE; ACTIVATION; EXPRESSION; TISSUE; STRAINS; CYTOSKELETON;

D O I：

10.1016/j.chom.2022.10.001

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Upon pathogen detection, macrophages normally stay sessile in tissues while dendritic cells (DCs) migrate to secondary lymphoid tissues. The obligate intracellular protozoan Toxoplasma gondii exploits the trafficking of mononuclear phagocytes for dissemination via unclear mechanisms. We report that, upon T. gondii infection, macrophages initiate the expression of transcription factors normally attributed to DCs, upregulate CCR7 expression with a chemotactic response, and perform systemic migration when adoptively transferred into mice. We show that parasite effector GRA28, released by the MYR1 secretory pathway, cooperates with host chromatin remodelers in the host cell nucleus to drive the chemotactic migration of parasitized macrophages. During in vivo challenge studies, bone marrow-derived macrophages infected with wild-type T. gondii outcompeted those challenged with MYR1- or GRA28-deficient strains in migrating and reaching secondary organs. This work reveals how an intracellular parasite hijacks chemotaxis in phagocytes and highlights a remarkable migratory plasticity in differentiated cells of the mononuclear phagocyte system.

引用

页码：1570 / +

页数：26