Jan Naujoks

Jan Naujoks
Bayer AG, Berlin, Germany · Target Discovery Technologies

PhD

About

47
Publications
6,115
Reads
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360
Citations
Additional affiliations
April 2017 - present
Bayer AG, Berlin, Germany
Position
  • Researcher
January 2016 - March 2017
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Position
  • Fellow
July 2014 - December 2015
Charité Universitätsmedizin Berlin
Position
  • Research Associate
Education
August 2007 - December 2007
Tulane University
Field of study
  • Biology
October 2003 - September 2009

Publications

Publications (47)
Article
Full-text available
IntroductionInflammation is a major pathological feature of pulmonary arterial hypertension (PAH), particularly in the context of inflammatory conditions such as systemic sclerosis (SSc). The endothelin system and anti-endothelin A receptor (ETA) autoantibodies have been implicated in the pathogenesis of PAH, and endothelin receptor antagonists are...
Article
Full-text available
The cyclic GMP-AMP synthase (cGAS)-STING pathway is central for innate immune sensing of various bacterial, viral and protozoal infections. Recent studies identified the common HAQ and R232H alleles of TMEM173/STING, but the functional consequences of these variants for primary infections are unknown. Here we demonstrate that cGAS- and STING-defici...
Data
Replication of L. pneumophila in murine WT and Tmem173-/- macrophages and IP-10 production. (A) WT and Tmem173-/- mouse BMDMs were infected with L. pneumophila at MOI 0.1, and bacterial loads were analyzed at the indicated time points. Data represent mean ± SEM of 5 independent experiments carried out in triplicates. (B) WT and STING-deficient BMDM...
Data
Cells from homozygous HAQ TMEM173/STING carriers are competent in responding to TLR7/8 activation. PBMCs from healthy volunteers (N = 3 for WT, N = 3 for HAQ) were isolated by density gradient centrifugation. 7 d after isolation cells were stimulated for 6 h with 1 ug/ml R848. RNA was isolated and the expression of IFNB and IL1B was determined by q...
Data
Carriage of the R232H TMEM173/STING allele does not affect replication of L. pneumophila in human cells. PBMCs from healthy volunteers (N = 3 for WT, N = 3 for R232H) were isolated by density gradient centrifugation. 7 d after isolation, cells were infected with L. pneumophila at MOI 0.1 and bacterial numbers were counted at the indicated time poin...
Data
Cells from homozygous HAQ TMEM173/STING carriers are impaired in cytokine production in response to cGAMP, L. pneumophila, and bacterial DNA. (A-D) PBMCs from healthy volunteers (N = 4 for WT, N = 4 for HAQ) carrying the WT variant of the TMEM173/STING gene or the HAQ allele in homozygosity were isolated as described above and infected for 16 to 18...
Data
STING deficiency affects L. pneumophila-induced production of pro-inflammatory cytokines. (A-C) Cytokine protein production was assessed by sandwich ELISA of supernatants from WT and Tmeme173-/- BMDMs infected for 16–18 h with L. pneumophila JR32 WT. Analyses were performed through the Mann-Whitney U Test. Data represent mean ± SEM of 4 independent...
Data
siRNA-mediated inhibition of cGAS reduces type I IFN responses against L. pneumophila in murine macrophages. BMDMs were transfected with a control siRNA or a siRNA sequence targeting cGas 48 h prior to infection; the expression of (A) cGas, (B) Ifnb and (C) Irg1 was quantified by qRT-PCR and the input normalized to the average expression of Gapdh a...
Data
Replication of L. pneumophila in human macrophages is not affected by carriage of HAQ TMEM173/STING. PBMCs from healthy volunteers (N = 4, per group) were isolated by density gradient centrifugation. 7 d after isolation, cells were infected with L. pneumophila at MOI 0.1 and bacterial numbers were counted at the indicated time points. Data represen...
Data
Cells from heterozygous HAQ TMEM173/STING carriers are partially impaired in IFNB induction in response to cGAMP and L. pneumophila. (A-D) PBMCs from healthy volunteers (N = 7 for WT/WT, N = 7 for WT/HAQ) carrying the WT variant of the TMEM173/STING gene or the HAQ allele in heterozygosity were isolated as described above and infected for 6 h with...
Data
Carriage of the R232H TMEM173/STING affects production of pro-inflammatory cytokines following stimulation with bacterial CDN but not in response to Legionella infection or stimulation with DNA. (A-D) PBMCs from healthy volunteers (N = 3 for WT, N = 3 for R232H) carrying the WT or the R232H allele in homozygosity were isolated and infected for 16 t...
Data
Demographics of the Netherlands cohort. (DOCX)
Article
Full-text available
Pneumonia may be caused by a wide range of pathogens and is considered the most common infectious cause of death in humans. Murine acute lung infection models mirror human pathologies in many aspects and contribute to our understanding of the disease and the development of novel treatment strategies. Despite progress in other fields of tissue imagi...
Article
Legionella pneumophila is a facultative intracellular bacterium which can cause a severe pneumonia called Legionnaires' disease after inhalation of contaminated water droplets and replication in alveolar macrophages. The innate immune system is generally able to sense and -in most cases- control L. pneumophila infection. Comorbidities and genetic r...
Article
Pulmonary vascular hyperresponsiveness is a main characteristic of pulmonary arterial hypertension (PAH). In PAH patients, elevated levels of the vasoconstrictors thromboxane A2 (TXA2), endothelin (ET)-1 and serotonin further contribute to pulmonary hypertension. Protein kinase C (PKC) isozyme alpha (PKCα) is a known modulator of smooth muscle cell...
Article
Full-text available
Author Summary Numerous intracellular bacterial pathogens replicate in specialized vacuoles within macrophages. We systematically study the molecular mechanism and the impact of macrophage-intrinsic antibacterial defense. Using L . pneumophila , an important cause of pneumonia and model organism for intracellular bacteria, we found that type I and...
Data
Proportions of CD11c+ GFP+ (undepleted) cells in DTX treated chimeric mice. CD45.1 recipient mice were lethally irradiated and repopulated with a 1:1 mixture of bone-marrow cells from CD45.2 transgenic CD11c-DTR-GFP and Ifnar/Ifngr-/- or WT donor mice. (A) Repopulation with CD45.2 donor cells within CD45.1 recipient mice was assessed by flow cytome...
Data
Macrophage activation by IFNs restricts intracellular growth of L. pneumophila. (A-C) Intracellular growth of L. pneumophila ΔflaA in WT BMMs left untreated or treated with IFNβ, IFNγ or both 16–18 h prior to and during infection. (D) Intracellular growth of L. pneumophila wt and ΔflaA in WT and Ifnar-/- BMMs. Data represent mean + s.e.m. of 2 (B),...
Data
L. pneumophila restriction in macrophages is largely independent of IFN-driven cell death. Cell death of infected (GFP+) cells (A; gating strategy) in WT BMMs left untreated or treated with 50 U/ml IFNβ or IFNγ 16–18 h prior to and during infection (D), Ifnar-/- (B, C), and Rip3-/- (E) BMMs infected with L. pneumophila wt or ΔflaA expressing eGFP w...
Data
Proteins differentially targeted to the LCV upon IFNβ or IFNγ treatment. Quantitative proteomic analysis of LCVs isolated 2 h p.i. with L. pneumophila ΔflaA from BMMs left untreated or treated with 50 U/ml IFNβ or IFNγ 16–18 h prior to and during infection. Bar graphs show top 20 proteins with a significant higher (red) or lower (green) abundance a...
Data
Mitochondria stay in close proximity to intracellular L. pneumophila. Representative frames from time-lapse confocal imaging of mitotracker stained (red) WT BMMs infected with L. pneumophila ΔflaA expressing eGFP (green). Imaging starts approximately 2 h p.i.. White arrow points toward a single mitochondrion staying in close proximity of the intrac...
Data
Mitochondrial ROS production in L. pneumophila-infected cells is largely independent of type I IFN signalling and IRG1. WT BMMs transfected with siRNAs 24 h prior to infection (A), or WT and Ifnar-/- BMMs (B) were infected with eGFP-expressing L. pneumophila wt and proportions of mitochondrial ROS producing (MitoSOX+) cells were determined by flow...
Data
LCV proteome data of L. pneumophila-infected untreated BMMs. All host- and Legionella-derived proteins identified in samples of LCVs isolated from L. pneumophila-infected resting BMMs are listed. Tabular outline of total results of GO analyses of all identified host proteins for cellular component (CC; as depicted in Fig 3B), and biological process...
Data
Mitochondria stay in close proximity to intracellular L. pneumophila. Time-lapse confocal imaging of mitotracker stained (red) WT BMMs infected with L. pneumophila ΔflaA expressing eGFP (green). Imaging starts approximately 2 h p.i. and single frames were taken every minute. See also S8 Fig. (AVI)
Data
Proteins involved in metabolic processes and transport and localization are strongly enriched at LCVs. GO enrichment analysis for biological processes (BP) of the 2307 host proteins identified in untreated LCV samples using BiNGO (Cytoscape). Hierarchical structure, read from inside (first node, blue encircled) to outside (final nodes, pink encircl...
Data
In vivo transcriptome data of L. pneumophila-infected wild-type and IFN-receptor knock-out mice. Tabular outline of all genes significantly up- or down-regulated in WT mice upon L. pneumophila infection and their regulation in Ifnar-/-, Ifngr-/- and Ifnar/Ifngr-/- mice upon infection. (XLSX)
Data
TaqMan assays and primer sets used for quantitative real-time PCR in this study. (DOCX)
Data
L. pneumophila restriction in macrophages is largely independent of RIP3, caspase-11 and iNOS. Intracellular growth of L. pneumophila wt and ΔflaA in WT, Rip3-/- (A, D), Casp11-/- (B, E) and Nos2-/- (C, F) BMMs left untreated (D-F) or treated with IFNβ or IFNγ 16–18 h prior and during infection (A-C). Data represent mean + s.e.m. of 2 (A, B, D, E)...
Data
IRG1 is transcriptionally regulated by type I and type II IFNs. Irg1 gene expression in WT BMMs left untreated or treated with 50 U/ml IFNβ or IFNγ for 16–18 h was determined by qRT-PCR. Data are mean + s.e.m. of 2 independent experiments done in triplicates. (PDF)
Data
LCV proteome data untreated compared to IFN-treated BMMs. Quantification of host-derived proteins identified in samples of LCVs from resting BMMs against LCVs from IFN-treated BMMs as well as quantification of proteins from LCVs of IFNβ against IFNγ treated BMMs. (XLSX)
Data
Oligonucleotides used for RNAi in this study. (DOCX)
Article
Full-text available
Lung-protective ventilation reduced acute respiratory distress syndrome (ARDS) mortality. To minimize ventilator-induced lung injury (VILI), tidal volume is limited, high plateau pressures are avoided, and positive end-expiratory pressure (PEEP) is applied. However, the impact of specific ventilatory patterns on VILI is not well defined. Increasing...
Thesis
Die hier vorgestellte Studie untersucht systematisch die angeborene Immunabwehr gegen L. pneumophila auf Ebene des gesamten Wirtsorganismus, sowie auf molekularer Ebene in Alveolar- und Knochenmarksmakrophagen. Mittels in vivo Transkriptomanalysen werden Typ I und II Interferone (IFN) als Hauptregulatoren der frühen pulmonalen Genexpression in der...
Article
Megaesophagus in mice has been associated with several genetic defects. In the present study we expand the range of genes associated with esophageal function and morphology by protein kinase C alpha (PKCα). PKCα-deficient mice showed a six times increased prevalence of megaesophagus at the age of 9-10 weeks compared to wild-type animals. In contras...
Article
Legionella pneumophila is a Gram-negative bacterium that can cause a severe pneumonia called Legionnaires' disease after inhalation of contaminated water droplets, replication in alveolar macrophages, and failure and/or subversion of innate resistance mechanisms. This innate immune defense depends on the different NOD-like receptors and the type II...
Article
Rationale: Lung protective ventilation in order to minimize ventilator-induced lung injury (VILI) reduced mortality in ARDS. Besides limiting tidal volumes, avoiding high plateau pressures and applying adequate levels of positive end expiratory pressure (PEEP), adjustment of ventilatory pattern aiming at lung protective ventilation is not defined t...
Article
Rationale: Lung protective ventilation in order to minimize ventilator-induced lung injury (VILI) reduced mortality in ARDS. Besides limiting tidal volumes, avoiding high plateau pressures and applying adequate levels of positive end expiratory pressure (PEEP), adjustment of ventilatory pattern aiming at lung protective ventilation is not defined t...
Chapter
The detection of bacterial pathogens by the innate immune system is mediated by various pattern recognition receptors that sense microbial molecules such as cell wall components, virulence factors or nucleic acids. Bacterial DNA is recognized by Toll-like receptor 9 (TLR9) at endosomal compartments and by cyclic GMP-AMP synthase, polymerase III/RIG...
Article
Full-text available
Several pathogenic bacteria utilize receptors of the CEACAM family to attach to human cells. Binding to different members of this receptor family can result in uptake of the bacteria. Uptake of Neisseria gonorrhoeae, a gram-negative human pathogen, via CEACAMs found on epithelial cells, such as CEACAM1, CEA or CEACAM6, differs mechanistically from...
Data
The amino-terminal SH2 domain of the regulatory subunit of class I PI3K associates with phosphorylated CEACAM1 and CEACAM3. 293 cells were transfected with HA-tagged CEACAM1 or GFP-tagged CEACAM3 constructs together with or without v-Src, a constitutive active protein tyrosine kinase. (A) CEACAM1-HA expressing cells were lysed and pulldown assays (...
Article
Defence mechanisms against intracellular bacterial pathogens are incompletely understood. Our study characterizes a type I IFN-dependent cell-autonomous defence pathway directed against Legionella pneumophila, an intracellular model organism and frequent cause of pneumonia. We show that macrophages infected with L. pneumophila produced IFNβ in a ST...

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