ppat.1006829.g005.tif (655.71 kB)
Endogenous R232H STING is partly deficient in sensing bacterial CDN but responds normally to Legionella infection or stimulation with DNA.
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posted on 2018-01-03, 18:40 authored by Juan S. Ruiz-Moreno, Lutz Hamann, Javeed A. Shah, Annelies Verbon, Frank P. Mockenhaupt, Monika Puzianowska-Kuznicka, Jan Naujoks, Leif E. Sander, Martin Witzenrath, John C. Cambier, Norbert Suttorp, Ralf R. Schumann, Lei Jin, Thomas R. Hawn, Bastian Opitz(A-D) PBMCs from healthy volunteers (N = 3 for WT and N = 3 for R232H) were isolated by density gradient centrifugation. 7 d after isolation cells were infected for 6 h with L. pneumophila at MOI 10 or stimulated for the same period with 1 ug/ml 2´-3´cGAMP, Rp-c-diAMPSS, cGMP or either bacterial DNA at a concentration of 1 ug/ml. RNA was isolated and the expression of IFNB (A), IL1B (B), and IL6 (C) and TNFA (D) was determined by qRT-PCR. Data are shown as the RQ of specified mRNAs. Data represent the mean ± SEM of 3 independent experiments carried out in triplicates. Differences were assessed with the Mann-Whitney U Test. Comparisons with a p < 0.05 were considered significant.
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R 232H attenuated cytokine productionsusceptibilitySTING-deficient murine macrophagesR 232H allelescyclic GMP-AMP synthaseSTING-deficient animalscyclic dinucleotidesTMEMIFNprotozoal infectionsRecent studiesHAQ STING variant impairs cGAS-dependentcGAS-STING cascadeLegionnairehaplotype frequencyDNATrial registration ClinicalTrials.gov DRKS 00005274CDNmouse modelwild-type miceLegionella pneumophilaresponsepro-inflammatory cytokines
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