Publikationsdatenbank

Perinatal dysfunction of innate immunity in cystic fibrosis (2025)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Jaudas, Florian

Bartenschlager, Florian (WE 12)

Shashikadze, Bachuki

Santamaria, Gianluca

Reichart, Daniel

Schnell, Alexander

Stöckl, Jan Bernd

Degroote, Roxane L.

Cambra, Josep M.

Graeber, Simon Y. (WE 6)

Bähr, Andrea

Kartmann, Heike

Stefanska, Monika

Liu, Huan

Naumann-Bartsch, Nora

Bruns, Heiko

Berges, Johannes

Hanselmann, Lea (WE 12)

Stirm, Michael

Krebs, Stefan

Deeg, Cornelia A.

Blum, Helmut

Schulz, Christian

Zawada, Dorota

Janda, Melanie

Caballero-Posadas, Ignacio

Kunzelmann, Karl

Moretti, Alessandra

Laugwitz, Karl-Ludwig

Kupatt, Christian

Saalmüller, Armin

Fröhlich, Thomas

Wolf, Eckhard

Mall, Marcus A. (WE 6)

Mundhenk, Lars (WE 12)

Gerner, Wilhelm

Klymiuk, Nikolai

Quelle

Science translational medicine : integrating medicine and science

Bandzählung: 17

Heftzählung: 782

Seiten: Artikelnummer eadk9145

ISSN: 1946-6242

Sprache

Englisch

Verweise

URL (Volltext): https://www.science.org/doi/10.1126/scitranslmed.adk9145

DOI: 10.1126/scitranslmed.adk9145

Pubmed: 39841805

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

In patients with cystic fibrosis (CF), repeated cycles of infection and inflammation eventually lead to fatal lung damage. Although diminished mucus clearance can be restored by highly effective CFTR modulator therapy, inflammation and infection often persist. To elucidate the role of the innate immune system in CF etiology, we investigated a CF pig model and compared these results with those for preschool children with CF. In newborn CF pigs, we observed changes in lung immune cell composition before the onset of infection that were dominated by increased monocyte infiltration, whereas neutrophil numbers remained constant. Flow cytometric and transcriptomic profiling revealed that the infiltrating myeloid cells displayed a more immature status. Cells with comparably immature transcriptomic profiles were enriched in the blood of CF pigs at birth as well as in preschool children with CF. This pattern coincided with decreased CD16 expression in the myeloid cells of both pigs and humans, which translated into lower phagocytic activity and reduced production of reactive oxygen species in both species. These results were indicative of a congenital, translationally conserved, and functionally relevant aberration of the immune system in CF. In newborn wild-type pigs, CFTR transcription in immune cells, including lung-derived and circulating monocytes, isolated from the bone marrow, thymus, spleen, and blood was below the detection limits of highly sensitive assays, suggesting an indirect etiology of the observed effects. Our findings highlight the need for additional immunological treatments to target innate immune deficits in patients with CF.