Toxoplasma gondiiinfection alters the recognition response of dendritic cells to stiffness substrate

Author:

Sun ZhePeng,Liu Jing,Zhu ZiFu,Ying Zhu,Zhou ZiHui,Liu QunORCID

Abstract

AbstractToxoplasma gondii(T.gondii) hijacks host immune cells as ‘Trojan Horse’, and the infected cells accelerated the parasites dissemination. During acute infection,T.gondiispecificity crosses the blood-brain-barrier to enter the brain. This selective mode of parasite transmission may be associated with the directed migration of infected immune cells. Immune cells follow various environmental cues for directional migration. However, the effect ofT.gondiiinfection on the recognition of mechanical cues by immune cells remains unknown. Here, we examined the adhesion and migration ofT.gondii-infected dendritic cells (DCs) on high and low stiffness substrates. We found thatT.gondiiinfection alters the durotaxis migration of DCs. Infected DC exhibited stronger adhesion and lower migration on low stiffness substrates. In contrast to uninfected DCs, infected DCs migrated towards the low stiffness environment. TgWIP and TgROP17 co-regulate the F-actin structure of DCs and are involved in the formation of abnormal F-actin filaments. Rearrangement of the F-actin structure resulting fromT.gondiiinfection regulates DCs’ abnormal recognition response to the mechanical cues. Recognition of DCs to the mechanical signals is independent of β2- integrin expression. Meanwhile, challenging DCs withT.gondiiincreased the phosphorylation of focal adhesion kinase (FAK). Treatment with a FAK inhibitor (VS- 6063) influences the recognition response of infected DCs. FAK inhibition in adoptively transferred infected DCs effectively prevents the dissemination ofT.gondiito the brain. The data reveal thatT.gondiiinfection inversely affects the durotaxis of DCs by altering the phosphorylation level of FAK and remodeling of F-actin structure.T.gondiiutilizes the change in DCs’ durotaxis migration to accelerate the parasites crossing the blood-brain-barrier.Author SummaryImmune cells travel through blood vessels and lymph vessels to various tissues, and respond to different types of environmental cues. Cells sense the cues and transmit these information to the cytoskeletal which induce directed cell migration towards or away from these signals.T.gondiiinfection remodeling the cytoskeletal of DCs which may cause abnormalities in these cues transduction. We found thatT.gondiiinfection induces the formation of abnormal F-actin filaments in DCs, TgWIP and TgROP17 co-regulate the DCs’ F-actin structure.T.gondiiinfection increased the phosphorylation of FAK in DCs and has no effect with DCs surface β2-integrin expression. These reasons lead to alter the original durotaxis migration of DCs, and makes infected-DCs tend to stay in the low stiffness environment. Meanwhile, the recognition response of infected DC to mechanical signal determines the parasite rapid crossing the blood-brain-barrier.

Publisher

Cold Spring Harbor Laboratory

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3