Stephan Dreschers
Boston Children's Hospital
P70-S6 Kinase 1Matrix metalloproteinaseInterleukin 19Internal medicineChemokineEndocrinologyInnate immune systemPeripheral blood mononuclear cellInternalizationCorpus albicansCellPhagocytosisIntrinsic apoptosisProinflammatory cytokineAndrologyReceptorGene knockdownTumor necrosis factor alphaKinaseChemistryInterleukin 10Cell typeSmall hairpin RNAApoptosisBystander effectImmunologyNeonatal sepsisT cellLeucineInflammationPhagocyteCD80SepsisCytokineADAM10LipopolysaccharideZymosanAmphiregulinCord bloodCandida albicansCD86FulminantMonocyteTLR2Clinical routineTissue homeostasisClinical courseFas receptorProgrammed cell deathSecretionCancer researchFlow cytometryMAPK/ERK pathwayBioinformaticsSignal transductionFas ligandInterleukin 8MedicineProtein kinase BPI3K/AKT/mTOR pathwayBiologyImmune systemMicrobiologyCell biologyCaspase
12Publications
6H-index
98Citations
Publications 12
Newest
MΦ differentiate from circulating monocytes (Mo). The reduced ability of neonatal Mo to undergo apoptosis after E. coli infection (phagocytosis-induced cell death (PICD)) could contribute to sustained inflammatory processes. The objective of our study was to investigate whether immune metabolism in Mo can be modified to gain access to pro-apoptotic signaling. To this end, we supplemented Mo from neonates and from adults with the branched amino acid leucine. In neonatal Mo, we observed increased ...
1 CitationsSource
#1Anke Seifert (RWTH Aachen University)H-Index: 3
#2Justyna Wozniak (RWTH Aachen University)H-Index: 3
Last. Andreas Ludwig (RWTH Aachen University)H-Index: 63
view all 9 authors...
Uptake of bacteria by phagocytes is a crucial step in innate immune defence. Members of the disintegrin and metalloproteinase (ADAM) family critically control the immune response by limited proteolysis of surface expressed mediator molecules. Here, we investigated the significance of ADAM17 and its regulatory adapter molecule iRhom2 for bacterial uptake by phagocytes. Inhibition of metalloproteinase activity led to increased phagocytosis of pHrodo labelled Gram-negative and -positive bacteria (E...
3 CitationsSource
#1Stephan Dreschers (Boston Children's Hospital)H-Index: 6
#2Kim Ohl (RWTH Aachen University)H-Index: 15
Last. Thorsten W. Orlikowsky (Boston Children's Hospital)H-Index: 16
view all 5 authors...
Neonatal sepsis is accompanied by impaired apoptotic depletion of monocytes and macrophages (MΦ), aberrant cytokine production, impaired cell metabolism, and sustained inflammation. Macrophage-colony stimulating factor (M-CSF) triggers the differentiation from monocytes into MΦ (MΦ-0). Interleukin-10 (IL10) and Interferon-gamma (IFNy) further differentiate MΦ subpopulations, the anti-inflammatory MΦ-IL10 and the pro-inflammatory MΦ-IFNy subtype. We previously have shown significant differences b...
7 CitationsSource
#1Christopher Platen (Boston Children's Hospital)H-Index: 4
#2Stephan Dreschers (Boston Children's Hospital)H-Index: 6
Last. Thorsten W. Orlikowsky (Boston Children's Hospital)H-Index: 16
view all 7 authors...
Neonates are extremely susceptible to bacterial infections, and evidences suggest that phagocytosis-induced cell death (PICD) is less frequently triggered in neonatal monocytes than in monocytes from adult donors. An insufficient termination of the inflammatory response, leading to a prolonged survival of neonatal monocytes with ongoing proinflammatory cytokine release, could be associated with the progression of various inflammatory diseases in neonates. Our previous data indicate that amphireg...
3 CitationsSource
#1Stephan Dreschers (Boston Children's Hospital)H-Index: 6
#2Christopher Platen (Boston Children's Hospital)H-Index: 4
Last. Thorsten W. Orlikowsky (Boston Children's Hospital)H-Index: 16
view all 6 authors...
Background: Cleaving ligands and receptors of the tumor necrosis factor (TNF) superfamily can critically regulate the induction of apoptosis. Matrix metalloproteinases (MMPs) such as MMP-9 and tumor necrosis factor-α-converting enzyme (TACE) have been shown to cleave CD95-Ligand (CD95L) and TNF/(TNF receptor-1) TNFR1 which induce phagocytosis induced cell death (PICD) in adult monocytes. This process is reduced in neonatal monocytes. Methods: Here we tested in vitro, whether Escherichia coli inf...
2 CitationsSource
#1Christopher Platen (Boston Children's Hospital)H-Index: 4
#2Stephan Dreschers (Boston Children's Hospital)H-Index: 6
Last. Thorsten W. Orlikowsky (Boston Children's Hospital)H-Index: 16
view all 5 authors...
Neonates are highly susceptible to microbial infections which is partially attributable to fundamental phenotypic and functional differences between effector cells of the adult and neonatal immune system. The resolution of the inflammation is essential to return to tissue homeostasis, but given that various neonatal diseases, such as periventricular leukomalacia, necrotizing enterocolitis, or bronchopulmonary dysplasia, are characterized by sustained inflammation, newborns seem predisposed to a ...
4 CitationsSource
#1Stephan Dreschers (Boston Children's Hospital)H-Index: 6
#2Christian GilleH-Index: 17
Last. Thorsten W. OrlikowskyH-Index: 16
view all 6 authors...
Phagocytosis-induced cell death (PICD) is diminished in cord blood monocytes (CBMO) as compared to cells from adults (PBMO) due to differences in the CD95-pathway. This may support a prolonged pro-inflammatory response with sequels of sustained inflammation as seen in neonatal sepsis. Here we hypothesized that TNF-α mediated induction of apoptosis is impaired in CBMO due to differences in the TNFR1-dependent internalization. Monocytes were infected with Escherichia coli-GFP (E. coli-GFP). Monocy...
10 CitationsSource
#1Stephan Dreschers (Boston Children's Hospital)H-Index: 6
#2Peter SauppH-Index: 1
Last. Thorsten W. OrlikowskyH-Index: 16
view all 7 authors...
BACKGROUND: Invasive fungal infections with Candida albicans (C. albicans) occur frequently in extremely low birthweight (ELBW) infants and are associated with poor outcome. Phagocytosis of C.albicans initializes apoptosis in monocytes (phagocytosis induced cell death, PICD). PICD is reduced in neonatal cord blood monocytes (CBMO). HYPOTHESIS: Phagocytosis of C. albicans causes PICD which differs between neonatal monocytes (CBMO) and adult peripheral blood monocytes (PBMO) due to lower stimulati...
7 CitationsSource
#1Christian GilleH-Index: 17
#2Stephan Dreschers (Boston Children's Hospital)H-Index: 6
Last. Thorsten W. OrlikowskyH-Index: 16
view all 11 authors...
The CD95/CD95L pathway is involved in phagocytosis-induced cell death of monocytes and may account for sustained inflammation in neonates
16 CitationsSource
#1Volker N. Umlauf (Boston Children's Hospital)H-Index: 1
#2Stephan DreschersH-Index: 6
Last. Thorsten W. OrlikowskyH-Index: 16
view all 3 authors...
Neonatal sepsis remains a burden problem by showing minimal initial symptoms of subtle character, nonspecific manifestation, and diagnostic pitfalls. The clinical course can be fulminant and fatal if treatment is not commenced promptly. It is therefore crucial to establish early diagnosis and initiate adequate therapy. Besides clinical symptoms, the most reliable laboratory markers in establishing diagnosis is currently the combined measurement of CRP and a cytokine (IL-6 and IL-8). Due to their...
27 CitationsSource