Flagellin nebulization enhances respiratory immune responses in the porcine model

Respiratory delivery of the Toll-like receptor 5-agonist FLAMOD, a recombinant flagellin, stimulates the airway epithelium, mobilizing immune cells and effectors in mouse models to combat respiratory infections, especially bacterial pneumonia. This study represents a comprehensive assessment of FLAMOD delivered by nebulization in pigs. A single nebulized dose was well tolerated with no adverse clinical effects. FLAMOD treatment led to immune cell infiltration in the lung tissue and granulocyte recruitment in conducting airways, as shown by histology and flow cytometry. RNA sequencing established immune activation across the respiratory tract, from the nose, trachea, and bronchi to the lungs, highlighting innate immunity, bacterial defense, cytokine and chemokine signaling, and granulocyte chemotaxis as key biological pathways. These findings demonstrate that FLAMOD stimulates a robust and common respiratory immunity, as well as compartment-specific response, providing a proof-of-concept for inhalation-based therapeutic strategies to combat bacterial pneumonia in the clinical setting.

Authors

Institutions

Publication Details

Journal
iScience
Published
2025-11-25
DOI
https://doi.org/10.1016/j.isci.2025.114218
Primary Topic
Immune Response and Inflammation
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Flagellin nebulization enhances respiratory immune responses in the porcine model

Nathalie Heuzé‐Vourc'h, Ignacio Caballero, Mara Baldry, Charlotte Costa et al.
iScience
Immune Response and Inflammation
article

Flagellin nebulization enhances respiratory immune responses in the porcine model

Nathalie Heuzé‐Vourc'h, Ignacio Caballero, Mara Baldry, Charlotte Costa, Delphine Beury, Norbert Stockhofe-Zurwieden, Delphine Cayet, Arndt Benecke, Ronan MacLoughlin, Jean‐Claude Sirard, David Hot, Lisette Ruuls, Yves Le Vern, Yasmine Zeroual
article en

Abstract

Respiratory delivery of the Toll-like receptor 5-agonist FLAMOD, a recombinant flagellin, stimulates the airway epithelium, mobilizing immune cells and effectors in mouse models to combat respiratory infections, especially bacterial pneumonia. This study represents a comprehensive assessment of FLAMOD delivered by nebulization in pigs. A single nebulized dose was well tolerated with no adverse clinical effects. FLAMOD treatment led to immune cell infiltration in the lung tissue and granulocyte recruitment in conducting airways, as shown by histology and flow cytometry. RNA sequencing established immune activation across the respiratory tract, from the nose, trachea, and bronchi to the lungs, highlighting innate immunity, bacterial defense, cytokine and chemokine signaling, and granulocyte chemotaxis as key biological pathways. These findings demonstrate that FLAMOD stimulates a robust and common respiratory immunity, as well as compartment-specific response, providing a proof-of-concept for inhalation-based therapeutic strategies to combat bacterial pneumonia in the clinical setting.

iScienceVol. 28(12)
Université de Tours (FR), Centre National de la Recherche Scientifique (FR), Inserm (FR), Université de Lille (FR), Université Paris-Seine (FR), Institut Pasteur de Lille (FR), Centre Hospitalier Universitaire de Lille (FR), Sorbonne Université (FR), Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR), Centre Hospitalier Universitaire de Tours (FR), Center for Infection and Immunity of Lille (FR), Groupe d'Oncologie Radiothérapie Tête et Cou (FR), Aerogen (Ireland) (IE), Services déconcentrés d'appui à la recherche Val de Loire (FR), Infectiologie et santé publique (FR), Institut de Biologie de Lille (FR), Neurosciences Paris-Seine (FR), Université Paris 1 Panthéon-Sorbonne (FR), Wageningen University & Research (NL)
Openalex Percentile: Top 60%
Immune Response and Inflammation
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.