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dc.contributor.authorLindenberg, Marc
dc.contributor.authorAlmeida, Luis
dc.contributor.authorDhillon-LaBrooy, Ayesha
dc.contributor.authorSiegel, Ekkehard
dc.contributor.authorHenriques-Normark, Birgitta
dc.contributor.authorSparwasser, Tim
dc.date.accessioned2021-03-30T11:20:34Z
dc.date.available2021-03-30T11:20:34Z
dc.date.issued2021-02-17
dc.identifier.citationJ Mol Med (Berl). 2021 Feb 17. doi: 10.1007/s00109-021-02039-5. Epub ahead of print.en_US
dc.identifier.pmid33595670
dc.identifier.doi10.1007/s00109-021-02039-5
dc.identifier.urihttp://hdl.handle.net/10033/622804
dc.description.abstractThe increasing prevalence of antimicrobial resistance in pathogens is a growing public health concern, with the potential to compromise the success of infectious disease treatments in the future. Particularly, the number of infections by macrolide antibiotics-resistant Streptococcus pneumoniae is increasing. We show here that Clarithromycin impairs both the frequencies and number of interleukin (IL)-17 producing T helper (Th) 17 cells within the lungs of mice infected with a macrolide-resistant S. pneumoniae serotype 15A strain. Subsequently, the tissue-resident memory CD4+ T cell (Trm) response to a consecutive S. pneumoniae infection was impaired. The number of lung resident IL-17+ CD69+ Trm was diminished upon Clarithromycin treatment during reinfection. Mechanistically, Clarithromycin attenuated phosphorylation of the p90-S6-kinase as part of the ERK pathway in Th17 cells. Moreover, a strong increase in the mitochondrial-mediated maximal respiratory capacity was observed, while mitochondrial protein translation and mTOR sisgnaling were unimpaired. Therefore, treatment with macrolide antibiotics may favor the spread of antimicrobial-resistant pathogens not only by applying a selection pressure but also by decreasing the natural T cell immune response. Clinical administration of macrolide antibiotics as standard therapy procedure during initial hospitalization should be reconsidered accordingly and possibly be withheld until microbial resistance is determined. KEY MESSAGES: • Macrolide-resistant S. pneumoniae infection undergoes immunomodulation by Clarithromycin • Clarithromycin treatment hinders Th17 and tissue-resident memory responses • Macrolide antibiotics impair Th17 differentiation in vitro by ERK-pathway inhibition.en_US
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectAnti-microbial resistanceen_US
dc.subjectClarithromycinen_US
dc.subjectMacrolide antibioticsen_US
dc.subjectStreptococcus pneumoniaeen_US
dc.subjectTh17 cellsen_US
dc.subjectTissue-resident memory T cellsen_US
dc.titleClarithromycin impairs tissue-resident memory and Th17 responses to macrolide-resistant Streptococcus pneumoniae infections.en_US
dc.typeArticleen_US
dc.identifier.eissn1432-1440
dc.contributor.departmentTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.en_US
dc.identifier.journalJournal of molecular medicine (Berlin, Germany)en_US
refterms.dateFOA2021-03-30T11:20:35Z
dc.source.journaltitleJournal of molecular medicine (Berlin, Germany)
dc.source.countryGermany


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