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, mrCSF-1 ImmunoTools Cat#12343115

D. Actinomycin and . Sigma-cat#a9415, , pp.50-76

. Mssafe-sigma-cat#mssafe, , p.1

, Disuccinimidyl suberate ThermoFisher Scientific Cat#21555, pp.68528-80

. Carbobenzoxy-leu-leu-leucinal, MG132) SIGMA Cat#M8699

, Oligonucleotides Primers for RT-qPCR: see Tables S1-S2 SIGMA N/A

. De-la-llave, Comité d'Ethique pour l'Expé rimentation Animale'' (CEEA) and protocols were approved by the ''Ministè re de l'Enseignement Supé rieur; Direction Gé né rale pour la Recherche et l'Innovation'' under number 2013-0047 and by the Animal Care and Use Committee at Institut Pasteur of Shanghai Animal Care. Isolation and Culture of Bone-Marrow-Derived Macrophages Bone marrow cell suspensions were recovered from tibias and femurs of BALB/c mice in DMEM medium (GIBCO, Life technologies) and cultured in medium complemented with mouse recombinant colony stimulating factor 1 (mrCSF-1, ImmunoTools, e1 EXPERIMENTAL MODEL AND SUBJECT DETAILS Ethics Statement Six-week-old female BALB/cJRj and Swiss nu/nu mice were purchased from Janvier, vol.30, pp.1870-1882, 2011.

. Lecoeur, Proteasomal protein degradation was studied in presence of 10 mM carbobenzoxy-Leu-Leu-Leucinal (MG132) during 4 hours. Parasite Isolation and BMDM Infection mCherry transgenic, tissue-derived amastigotes of Leishmania amazonensis strain LV79 (WHO reference number MPRO/BR/72/ M1841) were isolated from infected footpads of Swiss nude mice, Macrophage Cultures Inflammasome activity was analyzed after sequential treatment with 500 ng/ml LPS for 4 hours and 5 mM ATP for 2 hours, 2010.

, BMDMs were allowed to ingest heat-killed, tissue-derived amastigotes obtained after 20 min treatment at 45 C, or inert latex beads (5 mm particle size, Sigma-Aldrich) at a bead to macrophage ratio of 20:1. Phagocytic activity was determined using Texas redlabeled zymosan

, Mice were euthanized by carbon dioxide inhalation, footpads were removed and placed in Digestion Buffer (DB) composed of 50 U/ ml DNase I (Sigma-Aldrich), 100 U/ml collagenase II (Sigma-Aldrich), 100 U/ml collagenase IV (Sigma-Aldrich) and 1 U/ml dispase II (Roche Applied Science) in DMEM and placed on a 100 mm cell strainer. One ml of DB was perfused in the footpad at 5 different locations that were maintained at 37 C for 30 minutes, Generation of Ex Vivo Macrophages in BALB/c Nude Mice Infected macrophages were generated in the footpad of 5-7 week old female BALB/c nude mice (Balb/cRj-nu, JanvierLabs) infected by mCherry transgenic, tissue-derived amastigotes of Leishmania amazonensis, vol.4, pp.100-56142

, Relative protein expression was calculated by densitometric analysis (ImageJ software). Ratios between integrated density values obtained for the target protein and b-actin were calculated. Fold changes were expressed using the control sample (calibrator), with control values of uninfected / unstimulated samples being set to 1. RNA extraction and

. De-la-llave, qRT-PCR was carried out in 384-well PCR plates (Framestar 480/384, 4titude, Dominique Dutscher) using the iTaq Universal SYBRâ Green Supermix (Bio-Rad) and 0.5 mM primers with a LightCyclerâ 480 system, Total RNA isolation, 2011.

. Pfaffl, Nonparametric Kruskal-Wallis tests were performed on Log transformed Normalized Relative Quantity values. The modulation of macrophage RNA stability by L. am amastigotes was analyzed after Actinomycin D (AD, A9415, Sigma) treatment (5 mg/ml) in uninfected and infected samples stimulated with LPS. The modulation of RNA stability by L. am amastigotes was determined by comparing the FC values obtained between AD-treated versus AD-non treated cell samples, Heatmaps of the Fold-Changes on the log2 scale (qRT-PCR) and evaluation of the differences in H3 acetylation between infected and, 2011.

, Cytokine Quantitation in Culture Supernatants Cytokines were quantified in the supernatant using mouse instant ELISA kits (for IL-1b and TNF, eBioscience) or classical mouse ELISA kits for IL-1a (eBioscience) and IL-18

. Prina, Microscopic and Immunofluorescence Analyses BMDMs were seeded in complete medium containing 20 ng/ml mrCSF-1 either on glass slides (1.5x10 5 cells in 24-well plates or 5x10 4 cells in 96-well plates) per well. BMDMs were fixed / treated, 2004.

, Automated scoring of fluorescence signals was performed for (i) nuclear localization of p65 (RelA), (delineated by Hoechst 33342nuclear counter stain), and (ii) parasite detection using the mCherry signal, 25% gelatin and anti-F4/80 (MCA497 AbD Serotec)

. Arrigoni, Cells were washed with protein-free medium (34 C), fixed (1% methanol-free formaldehyde at 34 C, 10 min), incubated 10 min in 125 mM Glycine at 4 C. Cells were scraped into Nuclei EXtraction by SONication (NEXSON) buffer (5 mM PIPES pH 8, Chip Analysis, and qPCR BMDMs were seeded in 100 mm tissue culture dishes, 2016.

, Samples were sonicated in 1.5 mL Eppendorf tubes using the Bioruptor device (Diagenode) at ''low power'' with two cycles (30'' on 30'' off). Macrophage nuclei isolation was microscopically evaluated before collection of the nuclei by centrifugation (5 min, 4 C, 2000g) and resuspension in shearing buffer

, Chromatin was sheared into 100-500 bp fragments (three 5 min ultra-sound pulses, 4 C, sonicator set at ''high power''). Chromatin immunoprecipitations were performed with the EpiTectâ ChIP OneDay Kit (QIAGEN) using control IgGs and antibodies against acetylated histone H3 (H3K9/14ac) and tri-methylated H3K4 and H3K9 (diagenode). The EpiTectâ ChIP qPCR Array Mouse NF-kB Signaling Pathway was applied on (i) 1/100 of the input material before immunoprecipitation (positive control), (ii) negative control IgGs from normal non-immune serum (background assessment), and iii) H3ac fractions (epigenetic status for genes of the NF-kB pathway)