TcpC inhibits neutrophil extracellular trap formation by enhancing ubiquitination mediated degradation of peptidylarginine deiminase 4.

Nature Communications
Qian OuJian-Ping Pan

Abstract

TcpC is a multifunctional virulence factor of uropathogenic E. coli (UPEC). Neutrophil extracellular trap formation (NETosis) is a crucial anti-infection mechanism of neutrophils. Here we show the influence of TcpC on NETosis and related mechanisms. We show NETosis in the context of a pyelonephritis mouse model induced by TcpC-secreting wild-type E. coli CFT073 (CFT073wt) and LPS-induced in vitro NETosis with CFT073wt or recombinant TcpC (rTcpC)-treated neutrophils are inhibited. rTcpC enters neutrophils through caveolin-mediated endocytosis and inhibits LPS-induced production of ROS, proinflammatory cytokines and protein but not mRNA levels of peptidylarginine deiminase 4 (PAD4). rTcpC treatment enhances PAD4 ubiquitination and accumulation in proteasomes. Moreover, in vitro ubiquitination kit analyses show that TcpC is a PAD4-targetd E3 ubiquitin-ligase. These data suggest that TcpC inhibits NETosis primarily by serving as an E3 ligase that promotes degradation of PAD4. Our findings provide a novel mechanism underlying TcpC-mediated innate immune evasion.

References

Jun 26, 2004·Circulation Research·Miguel X van BemmelenHugues Abriel
Mar 28, 2009·Nature·Vijay G Bhoj, Zhijian J Chen
May 14, 2009·Nature Reviews. Molecular Cell Biology·Daniela Rotin, Sharad Kumar
Aug 25, 2010·The Journal of Experimental Medicine·Pingxin LiYanming Wang
Oct 27, 2010·The Journal of Cell Biology·Venizelos PapayannopoulosArturo Zychlinsky
Nov 27, 2010·Nucleic Acids Research·Aron Marchler-BauerStephen H Bryant
Jul 23, 2011·Nature Reviews. Molecular Cell Biology·Harvey T McMahon, Emmanuel Boucrot
Dec 14, 2011·Nature Reviews. Immunology·Xiaomo Jiang, Zhijian J Chen
Aug 21, 2012·Cell·Deepak NijhawanWilliam C Hahn
Apr 10, 2013·Proceedings of the National Academy of Sciences of the United States of America·Greg A SnyderTsan Sam Xiao
Nov 7, 2014·Nature Medicine·Doris PopovicIvan Dikic
Dec 6, 2014·Advances in Microbial Physiology·Petra Lüthje, Annelie Brauner
Jan 27, 2015·Nature Chemical Biology·Huw D LewisDavid M Wilson
Mar 3, 2015·Proceedings of the National Academy of Sciences of the United States of America·David Nobuhiro DoudaNades Palaniyar
Mar 26, 2016·Cell Research·Kirby N Swatek, David Komander
Mar 26, 2016·Cell Research·Hongbo Hu, Shao-Cong Sun
May 24, 2016·The Journal of Clinical Investigation·Anna WaldhuberThomas Miethke
Jun 1, 2016·Nature Reviews. Nephrology·Sarthak Gupta, Mariana J Kaplan
Aug 4, 2016·Nature Reviews. Molecular Cell Biology·Lori Buetow, Danny T Huang
Oct 4, 2016·Trends in Molecular Medicine·Lisa K McLellan, David A Hunstad
Dec 29, 2016·Translational Research : the Journal of Laboratory and Clinical Medicine·Patricia Ruiz-LimónNuria Barbarroja
Apr 5, 2017·Annual Review of Biochemistry·Ning Zheng, Nitzan Shabek
Sep 12, 2017·Frontiers in Cellular and Infection Microbiology·Giang T NguyenJoan Mecsas
Oct 11, 2017·Nature Reviews. Immunology·Venizelos Papayannopoulos
Feb 22, 2018·The Journal of Biological Chemistry·Thomas Mund, Hugh R Pelham
Mar 14, 2018·Developmental Cell·Gabriel SollbergerArturo Zychlinsky
Apr 16, 2018·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Mengze ZhouWentao Liu
Jun 12, 2018·Cell·Leonardo Almeida-SouzaHarvey T McMahon
Jul 20, 2018·Frontiers in Cellular and Infection Microbiology·Zayda FonsecaCarlos Rosales
Jul 25, 2018·Frontiers in Immunology·Eva GuiducciSalomé LeibundGut-Landmann
Sep 9, 2018·Nature Reviews. Molecular Cell Biology·Peter J Cullen, Florian Steinberg
Sep 16, 2018·Nature Communications·Elsa NeubertSebastian Kruss
Oct 27, 2018·Nature Reviews. Urology·Néha SihraSachin Malde
Dec 12, 2018·The Journal of Surgical Research·Kozo NomuraTetsuo Ohta
Dec 18, 2018·Cell Chemical Biology·Ingrid E Wertz, Xiaojing Wang

❮ Previous
Next ❯

Software Mentioned

ImageJ
Batch CD - Search
SPSS
R package edgeR

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences
Jian-Ping Pan, Xiao-Li Xin
European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery
N YoshimuraS Kido
International Journal of Medical Microbiology : IJMM
Sören SchubertErick Denamur
© 2021 Meta ULC. All rights reserved