Dataset Information

STAT6 Signaling Attenuates Interleukin-17-Producing ?? T Cells during Acute Klebsiella pneumoniae Infection.

ABSTRACT: ?? T cells are prevalent at mucosal and epithelial surfaces and are a critical first line of defense against bacterial and fungal pathogens. ??17 cells are a subset of ?? T cells which, in the presence of IL-23 and IL-1?, produce large quantities of interleukin-17A (IL-17A), a cytokine crucial to these cells' antibacterial and antifungal function. STAT6, an important transcription factor in Th2 differentiation and inhibition of Th1 differentiation, is expressed at high levels in the T cells of people with parasitic infections and asthma. Our group and others have shown that STAT6 attenuates IL-17A protein expression by CD4(+) T cells. By extension, we hypothesized that STAT6 activation also inhibits innate ??17 cell cytokine secretion. We show here that ??17 cells expressed the type I IL-4 receptor (IL-4R), and IL-4 increased STAT6 phosphorylation in ?? T cells. IL-4 inhibited ??17 cell production of IL-17A. IL-4 also decreased ??17 cell expression of IL-23R as well as Sgk1. To determine whether STAT6 signaling regulates ??17 cell numbers in vivo, we used a model of Klebsiella pneumoniae in mice deficient in STAT6. We chose K. pneumoniae for our in vivo model, since K. pneumoniae increases IL-17A expression and ??17 numbers. K. pneumoniae infection of STAT6 knockout mice resulted in a statistically significant increase in the number of ??17 cells compared to that of wild-type mice. These studies are the first to demonstrate that ??17 cells express the type I IL-4R and that STAT6 signaling negatively regulates ??17 cells, a cell population that plays a front-line role in mucosal immunity.

SUBMITTER: Bloodworth MH

PROVIDER: S-EPMC4862712 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Publications

STAT6 Signaling Attenuates Interleukin-17-Producing γδ T Cells during Acute Klebsiella pneumoniae Infection.

Bloodworth Melissa H MH Newcomb Dawn C DC Dulek Daniel E DE Stier Matthew T MT Cephus Jacqueline Y JY Zhang Jian J Goleniewska Kasia K Kolls Jay K JK Peebles R Stokes RS

Infection and immunity 20160422 5

γδ T cells are prevalent at mucosal and epithelial surfaces and are a critical first line of defense against bacterial and fungal pathogens. γδ17 cells are a subset of γδ T cells which, in the presence of IL-23 and IL-1β, produce large quantities of interleukin-17A (IL-17A), a cytokine crucial to these cells' antibacterial and antifungal function. STAT6, an important transcription factor in Th2 differentiation and inhibition of Th1 differentiation, is expressed at high levels in the T cells of p ...[more]

PMID: 26953325

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Project description:BACKGROUND: Carbapenemase producing Enterobacteriaceae are becoming a major public health concern globally, however, relatively little is known about the molecular and clinical epidemiology of these organisms in many parts of the world. METHODS: As part of a laboratory surveillance programme, 96 carbapenem non-susceptible Enterobacteriaceae isolates from clinical samples from patients in seven hospitals were referred for investigation for carbapenemases. Using polymerase chain reaction (PCR) to screen for a collection of genes encoding carbapenemases, 33 of 96 (34.5%) isolates were confirmed as carbapenemase producers. NDM-1 producers were the most prevalent at 64% (21/33) whilst OXA-181 was the second most common carbapenemase constituting 24.5% (8/33) of the carbapenemase producing isolates. Seven of these eight OXA-181 positive isolates underwent further characterisation with screening for other transmissible antimicrobial resistance determinants using PCR. Clonal relatedness was explored using Multilocus sequence typing (MLST) and Pulsed Field Gel Electrophoresis (PFGE). Plasmid characterisation was performed including restriction analysis and transfer by conjugation or transformation. RESULTS: In addition to the OXA-181 gene, all contained other transmissible resistance determinants including extended spectrum ?-lactamases, oxacillinases or 16S rRNA methylase genes, but none contained metallo-?-lactamases or serine carbapenemases. All isolates had a multidrug resistant phenotype with two isolates being resistant to every antibiotic tested including colistin. Multilocus sequence typing confirmed five isolates belonged to ST17 and two to ST14, with those belonging to the same sequence type having identical PFGE profiles. The OXA-181 gene was typically carried on large plasmids which were mostly non-conjugative. CONCLUSIONS: OXA-181 carbapenemase appears to be an important and probably under-recognised cause of carbapenem resistance in Enterobacteriaceae in Singapore. Further coordinated research into clinical and molecular epidemiology of carbapenemases is urgently required in Singapore and throughout Asia.

Dataset Information

STAT6 Signaling Attenuates Interleukin-17-Producing ?? T Cells during Acute Klebsiella pneumoniae Infection.

Publications

STAT6 Signaling Attenuates Interleukin-17-Producing γδ T Cells during Acute Klebsiella pneumoniae Infection.

Similar Datasets

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