Bacterial Nucleotidyl Cyclase Inhibits the Host Innate Immune Response by Suppressing TAK1 Activation.

Abstract:

:Exoenzyme Y (ExoY) is a type III secretion system effector found in 90% of the Pseudomonas aeruginosa isolates. Although it is known that ExoY is a soluble nucleotidyl cyclase that increases the cytoplasmic levels of nucleoside 3',5'-cyclic monophosphates (cNMPs) to mediate endothelial Tau phosphorylation and permeability, its functional role in the innate immune response is still poorly understood. Transforming growth factor β-activated kinase 1 (TAK1) is critical for mediating Toll-like receptor (TLR) signaling and subsequent activation of NF-κB and AP-1, which are transcriptional activators of innate immunity. Here, we report that ExoY inhibits proinflammatory cytokine production through suppressing the activation of TAK1 as well as downstream NF-κB and mitogen-activated protein (MAP) kinases. Mice infected with ExoY-deficient P. aeruginosa had higher levels of tumor necrosis factor (TNF) and interleukin-6 (IL-6), more neutrophil recruitment, and a lower bacterial load in lung tissue than mice infected with wild-type P. aeruginosa Taken together, our findings identify a previously unknown mechanism by which P. aeruginosa ExoY inhibits the host innate immune response.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

He C,Zhou Y,Liu F,Liu H,Tan H,Jin S,Wu W,Ge B

doi

10.1128/IAI.00239-17

subject

Has Abstract

pub_date

2017-08-18 00:00:00

issue

9

eissn

0019-9567

issn

1098-5522

pii

IAI.00239-17

journal_volume

85

pub_type

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