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DNases improve effectiveness of antibiotic treatment in murine polymicrobial sepsis

IntroductionNeutrophil extracellular traps (NETs) have various beneficial and detrimental effects in the body. It has been reported that some bacteria may evade the immune system when entangled in NETs. Thus, the aim of the current study was to evaluate the effects of a combined DNase and antibiotic...

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Hauptverfasser: Willemsen, Jan-Fritjof (VerfasserIn) , Wenskus, Julia (VerfasserIn) , Lenz, Moritz (VerfasserIn) , Rhode, Holger (VerfasserIn) , Trochimiuk, Madgalena (VerfasserIn) , Appl, Birgit (VerfasserIn) , Pagarol-Raluy, Laia (VerfasserIn) , Börnigen, Daniela (VerfasserIn) , Bang, Corinna (VerfasserIn) , Reinshagen, Konrad (VerfasserIn) , Herrmann, Martin (VerfasserIn) , Elrod, Julia (VerfasserIn) , Boettcher, Michael (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2024
In: Frontiers in immunology
Year: 2024, Jahrgang: 14, Pages: 1-10
ISSN:1664-3224
DOI:10.3389/fimmu.2023.1254838
Online-Zugang:Resolving-System, kostenfrei, Volltext: https://doi.org/10.3389/fimmu.2023.1254838
Verlag, kostenfrei, Volltext: https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1254838
Volltext
Verfasserangaben:Jan-Fritjof Willemsen, Julia Wenskus, Moritz Lenz, Holger Rhode, Madgalena Trochimiuk, Birgit Appl, Laia Pagarol-Raluy, Daniela Börnigen, Corinna Bang, Konrad Reinshagen, Martin Herrmann, Julia Elrod and Michael Boettcher
Beschreibung
Zusammenfassung:IntroductionNeutrophil extracellular traps (NETs) have various beneficial and detrimental effects in the body. It has been reported that some bacteria may evade the immune system when entangled in NETs. Thus, the aim of the current study was to evaluate the effects of a combined DNase and antibiotic therapy in a murine model of abdominal sepsis.MethodsC57BL/6 mice underwent a cecum-ligation-and-puncture procedure. We used wild-type and knockout mice with the same genetic background (PAD4-KO and DNase1-KO). Mice were treated with (I) antibiotics (Metronidazol/Cefuroxime), (II) DNAse1, or (III) with the combination of both; mock-treated mice served as controls. We employed a streak plate procedure and 16s-RNA analysis to evaluate bacterial translocation and quantified NETs formation by ELISA and immune fluorescence. Western blot and proteomics analysis were used to determine inflammation.ResultsA total of n=73 mice were used. Mice that were genetically unable to produce extended NETs or were treated with DNases displayed superior survival and bacterial clearance and reduced inflammation. DNase1 treatment significantly improved clearance of Gram-negative bacteria and survival rates. Importantly, the combination of DNase1 and antibiotics reduced tissue damage, neutrophil activation, and NETs formation in the affected intestinal tissue.ConclusionThe combination of antibiotics with DNase1 ameliorates abdominal sepsis. Gram-negative bacteria are cleared better when NETs are cleaved by DNase1. Future studies on antibiotic therapy should be combined with anti-NETs therapies.
Beschreibung:Published: 08 January 2024
Gesehen am 26.02.2024
Beschreibung:Online Resource
ISSN:1664-3224
DOI:10.3389/fimmu.2023.1254838

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