Clarithromycin impairs tissue-resident memory and Th17 responses to macrolide-resistant Streptococcus pneumoniae infections.
dc.contributor.author | Lindenberg, Marc | |
dc.contributor.author | Almeida, Luis | |
dc.contributor.author | Dhillon-LaBrooy, Ayesha | |
dc.contributor.author | Siegel, Ekkehard | |
dc.contributor.author | Henriques-Normark, Birgitta | |
dc.contributor.author | Sparwasser, Tim | |
dc.date.accessioned | 2021-03-30T11:20:34Z | |
dc.date.available | 2021-03-30T11:20:34Z | |
dc.date.issued | 2021-02-17 | |
dc.identifier.citation | J Mol Med (Berl). 2021 Feb 17. doi: 10.1007/s00109-021-02039-5. Epub ahead of print. | en_US |
dc.identifier.pmid | 33595670 | |
dc.identifier.doi | 10.1007/s00109-021-02039-5 | |
dc.identifier.uri | http://hdl.handle.net/10033/622804 | |
dc.description.abstract | The 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.iso | en | en_US |
dc.publisher | Springer | en_US |
dc.rights | Attribution 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Anti-microbial resistance | en_US |
dc.subject | Clarithromycin | en_US |
dc.subject | Macrolide antibiotics | en_US |
dc.subject | Streptococcus pneumoniae | en_US |
dc.subject | Th17 cells | en_US |
dc.subject | Tissue-resident memory T cells | en_US |
dc.title | Clarithromycin impairs tissue-resident memory and Th17 responses to macrolide-resistant Streptococcus pneumoniae infections. | en_US |
dc.type | Article | en_US |
dc.identifier.eissn | 1432-1440 | |
dc.contributor.department | TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany. | en_US |
dc.identifier.journal | Journal of molecular medicine (Berlin, Germany) | en_US |
refterms.dateFOA | 2021-03-30T11:20:35Z | |
dc.source.journaltitle | Journal of molecular medicine (Berlin, Germany) | |
dc.source.country | Germany |