Publikationsdatenbank

Trimodulin supports antibacterial defence and restricts inflammation in preclinical pneumonia models (2025)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Nouailles, Geraldine

Bischoff, Romina

Linke, Kerstin

Taylor, Alexander

Gutbier, Birgitt

Pennitz, Peter

Goekeri, Cengiz

Kunder, Sandra (WE 12)

Voß, Anne (WE 12)

Brömel, Theresa C.

Kershaw, Olivia (WE 12)

Milek, Miha

Farztdinov, Vadim

Mülleder, Michael

Weissmüller, Sabrina

Heinz, Corina C.

Visser, Mayken

Bohlaender, Fabian

Ahrens, Katharina

Beule, Dieter

Gruber, Achim D. (WE 12)

Koenig, Martin

Witzenrath, Martin

Quelle

The European respiratory journal

Bandzählung: AOP

Seiten: 2500392

ISSN: 0903-1936

Sprache

Englisch

Verweise

URL (Volltext): https://publications.ersnet.org/lookup/doi/10.1183/13993003.00392-2025

DOI: 10.1183/13993003.00392-2025

Pubmed: 40935582

Kontakt

Institut für Tierpathologie

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

Abstract / Zusammenfassung

Background

Severe pneumonia (sCAP) remains a global health challenge with high mortality despite advances in antibiotic therapy and supportive care. Immunoglobulin (Ig) therapies, especially IgM-containing ones, have shown promise in enhancing host defence and reducing inflammation. The CIGMA trial highlighted trimodulin's potential to lower mortality of sCAP patients with high C-reactive protein and low IgM levels.

Methods

We investigated the protective effects of trimodulin on clinical status, bacterial burden, lung integrity, and inflammatory responses in murine models of lung injury, including both ventilator-induced lung injury (VILI) and infection-induced models with non-sterile inflammation.

Findings

In mice, trimodulin significantly protected against lethal pneumococcal pneumonia by reducing bacterial burden and disease severity while preserving alveolar barrier integrity and limiting lung edema. The antibacterial action of trimodulin was mediated through opsonophagocytosis, and its anti-inflammatory effects operated independently of the latter. When combined with ampicillin, trimodulin exhibited enhanced suppression of inflammation.

Interpretation

Our findings in preclinical pneumonia models suggest that trimodulin could be a promising therapy for sCAP patients. We provide evidence that trimodulin enhances host defence, reduces detrimental pulmonary inflammation and barrier dysfunction, and limits pulmonary edema, which may explain its beneficial effects observed in sCAP patients.