Human innate lymphoid cell activation by adenoviruses is modified by host defence proteins and neutralizing antibodies

Author:

Paris OcéaneORCID,Mennechet Franck JD,Kremer EJORCID

Abstract

AbstractInnate lymphoid cells (ILCs), the complements of diverse CD4 T helper cells, help maintain tissue homeostasis by providing a link between innate and adaptive immune responses. While pioneering studies over the last decade have advanced our understanding how ILCs influence adaptive immune responses to pathogens, far less is known about whether the adaptive immune response feeds back into an ILC response. In this study, we isolated ILCs from blood of healthy donors, fine-tuned culture conditions, and then directly challenged them with human adenoviruses (HAdVs), with HAdVs and host defence proteins (HDPs) or neutralizing antibodies (NAbs), to mimic interactions in a host with pre-existing immunity. Additionally, we developed anex vivoapproach to identify how bystander ILCs respond to the uptake of HAdVs ± neutralizing antibodies by monocyte-derived dendritic cells. We show that ILCs take up HAdVs, which induces phenotypic maturation and cytokine secretion. Moreover, NAbs and HDPs complexes modified the cytokine profile generated by ILCs, consistent with a feedback loop for host antiviral responses and potential to impact adenovirus-based vaccine efficacy.Author SummarySeveral studies have shown the importance of innate lymphoid cells (ILCs) both from an immune and physiological point of view, in particular for their role in the maintenance of tissue integrity, pathogens clearance, or in the establishment of immune tolerance. Our study focuses on the role of ILCs during direct challenge with prototype vaccines based on human adenoviruses (HAdVs) ± host defence proteins (HDPs) or neutralizing antibodies (NAbs) to mimic interactions in a host with pre-existing immunity. In parallel, through an ex vivo approach we observe how bystander ILCs respond to the uptake of HAdVs ± NAbs by monocyte-derived dendritic cells. We show that ILCs take up HAdVs, which induces pro- inflammatory and antiviral responses through phenotypic maturation and cytokine secretion. Moreover, HAdV-NAb and HAdV-HDP complexes modified the cytokine profile generated by ILCs, consistent with a feedback loop for host antiviral responses and potential to impact HAdV vaccine efficacy.

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