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Transcriptome sequencing of human neutrophil

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. In situ NETosis of kidneys from pyelonephritis mouse model induced by TcpC-secreting wild-type CFT073 (CFT073wt) and LPS-induced in vitro NETosis in 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 suggest 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE173807 | GEO | 2021/05/05

REPOSITORIES: GEO

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NET formation is a default epigenetic program controlled by PAD4 in apoptotic neutrophils

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