Systematic P2Y receptor survey identifies P2Y11 as modulator of immune responses and virus replication in macrophages

Author:

Andersen Line Lykke1ORCID,Huang Yiqi1ORCID,Urban Christian1ORCID,Oubraham Lila1,Winheim Elena2ORCID,Stafford Che3,Nagl Dennis3,O'Duill Fionan3,Ebert Thomas3ORCID,Engleitner Thomas4,Paludan Søren Riis56ORCID,Krug Anne2ORCID,Rad Roland4ORCID,Hornung Veit3ORCID,Pichlmair Andreas167ORCID

Affiliation:

1. Institute of Virology, School of Medicine Technical University of Munich Munich Germany

2. Institute of Immunology, Biomedical Center Ludwig‐Maximilians‐Universität München Munich Germany

3. Department of Biochemistry, Gene Center Munich Ludwig‐Maximilians‐Universität München Munich Germany

4. Institute of Molecular Oncology and Functional Genomics, School of Medicine Technical University of Munich Munich Germany

5. Department of Biomedicine Aarhus University Aarhus Denmark

6. Center of immunology of viral infection (CiViA) Aarhus University Aarhus Denmark

7. German Center for Infection Research (DZIF), Munich Partner Site Munich Germany

Abstract

AbstractThe immune system is in place to assist in ensuring tissue homeostasis, which can be easily perturbed by invading pathogens or nonpathogenic stressors causing tissue damage. Extracellular nucleotides are well known to contribute to innate immune signaling specificity and strength, but how their signaling is relayed downstream of cell surface receptors and how this translates into antiviral immunity is only partially understood. Here, we systematically investigated the responses of human macrophages to extracellular nucleotides, focusing on the nucleotide‐sensing GPRC receptors of the P2Y family. Time‐resolved transcriptomic analysis showed that adenine‐ and uridine‐based nucleotides induce a specific, immediate, and transient cytokine response through the MAPK signaling pathway that regulates transcriptional activation by AP‐1. Using receptor trans‐complementation, we identified a subset of P2Ys (P2Y1, P2Y2, P2Y6, and P2Y11) that govern inflammatory responses via cytokine induction, while others (P2Y4, P2Y11, P2Y12, P2Y13, and P2Y14) directly induce antiviral responses. Notably, P2Y11 combined both activities, and depletion or inhibition of this receptor in macrophages impaired both inflammatory and antiviral responses. Collectively, these results highlight the underappreciated functions of P2Y receptors in innate immune processes.

Funder

Elitenetzwerk Bayern

Deutsche Forschungsgemeinschaft

European Research Council

Publisher

Springer Science and Business Media LLC

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,Molecular Biology,General Neuroscience

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