Hier finden Sie wissenschaftliche Publikationen aus den Fraunhofer-Instituten.

Induction of innate immune response in fresh human lung tissue ex vivo following P. aeruginosa infection

: Müller, Laura; Kraemer, Nadine; Braubach, Peter; Jonigk, Danny; Fieguth, Hans-Gerd; Pfennig, Olaf; Bersch, Claus; Braun, Armin; Sewald, Katherina; Wronski, Sabine


European Respiratory Journal 52 (2018), Supplement 62, Abstract PA4615
ISSN: 0903-1936
ISSN: 1399-3003
European Respiratory Society (ERS International Congress) <2018, Paris>
Fraunhofer ITEM ()

Cystic fibrosis patients are highly susceptible to Pseudomonas aeruginosa which rapidly adapts to the lung microenvironment and causes chronic inflammation strongly contributing to disease pathogenesis. In the presented study, fresh human lung tissue was infected ex vivo with P. aeruginosa to investigate bacterial adaption to lung tissue and antibiotic treatment as well as the host immune response. Human lung tissue slices were infected with 105 PAO1, treated with 10, 20 or 40µg/ml tobramycin and incubated for 24h or 96h. Tissue viability was assessed by Calcein AM staining. Bacterial load was determined by dilution plating and enumeration of CFU. Bacterial colonization was imaged by confocal microscopy. Cytokine release was determined using ELISA.P. aeruginosa rapidly colonized the lung tissue and induced a strong and persistent host immune response as indicated by the release of IL-8, IL-6, IL-1ß and TNF-α. Tobramycin treatment reduced CFU and resulted in maintained tissue viability, but without full eradication of P. aeruginosa, thereby enabling the transition to persisting infection up to 96h. Interestingly, this adaption of P. aeruginosa was associated with a decreased sensitivity to repeated antibiotic treatment. In summary, P. aeruginosa infection and respective induction of the host immune response can be reflected in human lung tissue ex vivo. Furthermore, the data indicate that early stages of the transition of acute to persistent infection can be mimicked, thereby reflecting bacterial adaption to antibiotic treatment. This paves the way to future investigations on host-pathogen interactions as well as testing of novel anti-infective or immunomodulatory therapeutics.