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dc.contributor.authorBöning, Martha A L
dc.contributor.authorParzmair, Gerald P
dc.contributor.authorJeron, Andreas
dc.contributor.authorDüsedau, Henning P
dc.contributor.authorKershaw, Olivia
dc.contributor.authorXu, Baolin
dc.contributor.authorRelja, Borna
dc.contributor.authorSchlüter, Dirk
dc.contributor.authorDunay, Ildiko Rita
dc.contributor.authorReinhold, Annegret
dc.contributor.authorSchraven, Burkhart
dc.contributor.authorBruder, Dunja
dc.date.accessioned2021-12-01T13:20:06Z
dc.date.available2021-12-01T13:20:06Z
dc.date.issued2021-09-30
dc.identifier.citationFront Immunol. 2021 Sep 30;12:724855. doi: 10.3389/fimmu.2021.724855.en_US
dc.identifier.pmid34659211
dc.identifier.doi10.3389/fimmu.2021.724855
dc.identifier.urihttp://hdl.handle.net/10033/623107
dc.description.abstractThe adhesion and degranulation-promoting adaptor protein (ADAP) serves as a multifunctional scaffold and is involved in the formation of immune signaling complexes. To date, only limited data exist regarding the role of ADAP in pathogen-specific immunity during in vivo infection, and its contribution in phagocyte-mediated antibacterial immunity remains elusive. Here, we show that mice lacking ADAP (ADAPko) are highly susceptible to the infection with the intracellular pathogen Listeria monocytogenes (Lm) by showing enhanced immunopathology in infected tissues together with increased morbidity, mortality, and excessive infiltration of neutrophils and monocytes. Despite high phagocyte numbers in the spleen and liver, ADAPko mice only inefficiently controlled pathogen growth, hinting at a functional impairment of infection-primed phagocytes in the ADAP-deficient host. Flow cytometric analysis of hallmark pro-inflammatory mediators and unbiased whole genome transcriptional profiling of neutrophils and inflammatory monocytes uncovered broad molecular alterations in the inflammatory program in both phagocyte subsets following their activation in the ADAP-deficient host. Strikingly, ex vivo phagocytosis assay revealed impaired phagocytic capacity of neutrophils derived from Lm-infected ADAPko mice. Together, our data suggest that an alternative priming of phagocytes in ADAP-deficient mice during Lm infection induces marked alterations in the inflammatory profile of neutrophils and inflammatory monocytes that contribute to enhanced immunopathology while limiting their capacity to eliminate the pathogen and to prevent the fatal outcome of the infection.en_US
dc.language.isoenen_US
dc.publisherFrontiersen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectADAPen_US
dc.subjectListeria monocytogenesen_US
dc.subjectadaptor proteinen_US
dc.subjectinflammatory monocytesen_US
dc.subjectneutrophil extracellular trapsen_US
dc.subjectneutrophilsen_US
dc.subjectphagocytosisen_US
dc.titleEnhanced Susceptibility of ADAP-Deficient Mice to Infection Is Associated With an Altered Phagocyte Phenotype and Function.en_US
dc.typeArticleen_US
dc.identifier.eissn1664-3224
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalFrontiers in immunologyen_US
dc.source.volume12
dc.source.beginpage724855
dc.source.endpage
refterms.dateFOA2021-12-01T13:20:07Z
dc.source.journaltitleFrontiers in immunology
dc.source.countrySwitzerland


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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International