Endogenous R232H STING is partly deficient in sensing bacterial CDN but responds normally to <i>Legionella</i> infection or stimulation with DNA. 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 10.1371/journal.ppat.1006829.g005 https://plos.figshare.com/articles/figure/Endogenous_R232H_STING_is_partly_deficient_in_sensing_bacterial_CDN_but_responds_normally_to_i_Legionella_i_infection_or_stimulation_with_DNA_/5755266 <p>(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 <i>L</i>. <i>pneumophila</i> 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 <i>IFNB</i> (A), <i>IL1B</i> (B), and <i>IL6</i> (C) and <i>TNFA</i> (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.</p> 2018-01-03 18:40:52 R 232H attenuated cytokine production susceptibility STING-deficient murine macrophages R 232H alleles cyclic GMP-AMP synthase STING-deficient animals cyclic dinucleotides TMEM IFN protozoal infections Recent studies HAQ STING variant impairs cGAS-dependent cGAS-STING cascade Legionnaire haplotype frequency DNA Trial registration ClinicalTrials.gov DRKS 00005274 CDN mouse model wild-type mice Legionella pneumophila response pro-inflammatory cytokines