Reversal of trauma-induced monocyte paralysis by IFN-γ fails to prevent ventilator-associated pneumonia, implicating lymphoid deficits in infection risk
Year: 2026
Type: article
Abstract: Ventilator-associated pneumonia (VAP) remains a frequent and severe complication in critically ill patients. Although interferon-gamma (IFN-γ) has been reported to restore trauma-associated immune defects, the PREV-HAP trial (ClinicalTrials.gov NCT04793568) did not show a benefit of IFN-γ on VAP prevention. To investigate the immunological basis of this therapeutic failure, we performed longitudinal high-dimensional immunoprofiling on 104 trial participants. IFN-γ improved phenotypic and metabolic features of monocyte immune suppression, most notably by increasing HLA-DR expression. Whereas HLA-DR on monocytes is a well-established biomarker for patient outcomes, its modulation via IFN-γ injection did not prevent lung pathology, possibly due to CCR7 induction. In contrast, we identified pre-existing deficits in T- and B-cell subsets in patients who subsequently developed VAP. Together, these findings suggest that monocytic HLA-DR expression reflects the immune status rather than directly influencing VAP susceptibility, and that lymphoid immune alterations may represent more relevant determinants of infection risk in ventilated patients.
Source: Nature Communications
Authors: Jonas Schmid, Susanne Unger, Athanasios Ziogas, Stefanie Kreutmair, Maud Mayoux, Can Ulutekin, Colin Sparano, Juan Villar-Vesga, Marijne Vermeer, Minqi Lin, Selma Tuzlak, Tobias Wertheimer, Daehong Kim, Stanislav Dergun, Boris Novakovic, Laura Hurtado-Navarro, Anaísa V. Ferreira, Mariolina Bruno, Marijana Saric, Julien Chabbey, Amir Elalfy, Vanessa Dobernig, Philipp Häne, Cécile Poulain, Fernando P. Canale, Bruno Francois, Mihai G. Netea, Antoine Roquilly, Burkhard Becher
Institutions: University of Zurich, Radboud University Medical Center, University Hospital Zurich, Royal Children's Hospital, The University of Melbourne, Murdoch Children's Research Institute, Inserm, Centre Hospitalier Universitaire de Nantes, Center for Research in Transplantation and Translational Immunology, Nantes Université, Centre Hospitalier Universitaire de Limoges, University of Bonn, Centre d'Investigation Clinique de Nantes
Language: English
Topic: Nosocomial Infections in ICU
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Jacques und Gloria Gossweiler-Stiftung, Joint Programming Initiative on Antimicrobial Resistance, European Commission, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Swiss Cancer Research Foundation, UZH Foundation, Horizon 2020 Framework Programme, National Health and Medical Research Council
OpenAlex ID: W7225000660