Natalia Muñoz-Wolf1,2, Analía Rial1, Delphine Fougeron3, Julien Tabareau3, Jean-Claude Sirard3, José A Chabalgoity1. 1. Departamento de Desarrollo Biotecnológico, Instituto de Higiene, Facultad de Medicina-Universidad de la República (UdelaR), Montevideo, 11600, Uruguay. 2. Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, D02 PN40, Ireland. 3. Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR8204 - CIIL - Center for Infection & Immunity of Lille, F-59000 Lille, France.
Abstract
AIM: To evaluate efficacy of sublingual flagellin to treat acute pneumonia. MATERIALS & METHODS: Mice were treated sublingually with flagellin and challenged intranasally with a lethal dose of pneumococcus. Flagellins lacking TLR5 or NLRC4 activation domains were used to assess their contribution to protection. RESULTS: Sublingual flagellin protected mice in a TLR5-dependent, NLRC4-independent fashion. Neutrophils were required for protection. Flagellin-stimulated lung epithelial cells recapitulated the lung's transcriptional profile suggesting they could be targeted by flagellin in vivo. CONCLUSION: Ligation of TLR5, a pathogen recognition receptor not naturally engaged by pneumococcus, protects mice from invasive pneumonia when administered via sublingual route. This can be a highly cost-effective alternative therapy against pneumonia.
AIM: To evaluate efficacy of sublingual flagellin to treat acute pneumonia. MATERIALS & METHODS:Mice were treated sublingually with flagellin and challenged intranasally with a lethal dose of pneumococcus. Flagellins lacking TLR5 or NLRC4 activation domains were used to assess their contribution to protection. RESULTS:Sublingual flagellin protected mice in a TLR5-dependent, NLRC4-independent fashion. Neutrophils were required for protection. Flagellin-stimulated lung epithelial cells recapitulated the lung's transcriptional profile suggesting they could be targeted by flagellin in vivo. CONCLUSION: Ligation of TLR5, a pathogen recognition receptor not naturally engaged by pneumococcus, protects mice from invasive pneumonia when administered via sublingual route. This can be a highly cost-effective alternative therapy against pneumonia.
Authors: Allison M Owen; Jessica B Fults; Naeem K Patil; Antonio Hernandez; Julia K Bohannon Journal: Front Immunol Date: 2021-02-18 Impact factor: 7.561