Publikationsdatenbank

IL-37 Causes Excessive Inflammation and Tissue Damage in Murine Pneumococcal Pneumonia (2017)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Schauer, Anja E

Klassert, Tilman E

von Lachner, Carolin

Riebold, Diana

Schneeweiß, Anne

Stock, Magdalena

Müller, Mario M

Hammerschmidt, Sven

Bufler, Philip

Seifert, Ulrike

Dietert, Kristina (WE 12)

Dinarello, Charles A

Nold, Marcel F

Gruber, Achim D (WE 12)

Nold-Petry, Claudia A

Slevogt, Hortense

Quelle

Journal of innate immunity; 9(4) — S. 403–418

ISSN: 1662-8128

Sprache

Englisch

Verweise

DOI: 10.1159/000469661

Pubmed: 28601872

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
Gebäude 12
14163 Berlin
+49 30 838 62450

Abstract / Zusammenfassung

Streptococcus pneumoniae infections can lead to severe complications with excessive immune activation and tissue damage. Interleukin-37 (IL-37) has gained importance as a suppressor of innate and acquired immunity, and its effects have been therapeutic as they prevent tissue damage in autoimmune and inflammatory diseases. By using RAW macrophages, stably transfected with human IL-37, we showed a 70% decrease in the cytokine levels of IL-6, TNF-α, and IL-1β, and a 2.2-fold reduction of the intracellular killing capacity of internalized pneumococci in response to pneumococcal infection. In a murine model of infection with S. pneumoniae, using mice transgenic for human IL-37b (IL-37tg), we observed an initial decrease in cytokine expression of IL-6, TNF-α, and IL-1β in the lungs, followed by a late-phase enhancement of pneumococcal burden and subsequent increase of proinflammatory cytokine levels. Additionally, a marked increase in recruitment of alveolar macrophages and neutrophils was noted, while TRAIL mRNA was reduced 3-fold in lungs of IL-37tg mice, resulting in necrotizing pneumonia with augmented death of infiltrating neutrophils, enhanced bacteremic spread, and increased mortality. In conclusion, we have identified that IL-37 modulates several core components of a successful inflammatory response to pneumococcal pneumonia, which lead to increased inflammation, tissue damage, and mortality.