Publikationsdatenbank

TNF superfamily member 14 drives post-influenza depletion of alveolar macrophages enabling secondary pneumococcal pneumonia (2025)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Malainou, Christina

Peteranderl, Christin

Ferrero, Maximiliano Ruben

Vazquez-Armendariz, Ana Ivonne

Alexopoulos, Ioannis

Franz, Katharina

Knippenberg, Klara

Better, Julian

Estiri, Mohammad

Wu, Cheng-Yu

Schultheis, Hendrik

Bushe, Judith

del Rio, Maria-Luisa

Rodriguez-Barbosa, Jose Ignacio

Pfeffer, Klaus

Günther, Stefan

Looso, Mario

Gruber, Achim Dieter (WE 12)

Vadász, István

Matt, Ulrich

Herold, Susanne

Quelle

The Journal of clinical investigation

Bandzählung: Online ahead of print

Seiten: e185390 AOP

ISSN: 0021-9738

Sprache

Englisch

Verweise

URL (Volltext): https://www.jci.org/articles/view/185390

DOI: 10.1172/JCI185390

Pubmed: 41252214

Kontakt

Institut für Tierpathologie

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

Abstract / Zusammenfassung

Secondary bacterial infection, often caused by Streptococcus pneumoniae (Spn), is one of the most frequent and severe complications of influenza A virus (IAV)-induced pneumonia. Phenotyping of the pulmonary immune cell landscape after IAV infection revealed a substantial depletion of the tissue-resident alveolar macrophage (TR-AM) population at day 7, which was associated with increased susceptibility to Spn outgrowth. To elucidate the molecular mechanisms underlying TR-AM depletion, and to define putative targets for treatment, we combined single-cell transcriptomics and cell-specific PCR profiling in an unbiased manner, using in vivo models of IAV infection and IAV/Spn co-infection. The TNF superfamily 14 (TNFSF14) ligand-receptor axis was revealed as the driving force behind post-influenza TR-AM death during the early infection phase, enabling the transition to pneumococcal pneumonia, while intrapulmonary transfer of genetically modified TR-AMs and antibody-mediated neutralization of specific pathway components alleviated disease severity. With a mainly neutrophilic expression and a high abundance in the bronchoalveolar fluid (BALF) of patients with severe virus-induced ARDS, TNFSF14 emerged as a key determinant of virus-driven lung injury. Targeting the TNFSF14-mediated intercellular communication network in the virus-infected lung can, therefore, improve host defense, minimizing the risk of subsequent bacterial pneumonia, and ameliorating disease outcome.