Sublingual flagellin protects against acute pneumococcal pneumonia in a TLR5-dependent and NLRC4-independent fashion

Natalia Muñoz-Wolf; Analía Rial; Delphine Fougeron; Julien Tabareau; Jean-Claude Sirard; José A Chabalgoity

doi:10.2217/fmb-2016-0045

Sublingual flagellin protects against acute pneumococcal pneumonia in a TLR5-dependent and NLRC4-independent fashion

Future Microbiol. 2016 Sep:11:1167-77. doi: 10.2217/fmb-2016-0045. Epub 2016 Aug 22.

Authors

Natalia Muñoz-Wolf^{1

2}, Analía Rial¹, Delphine Fougeron³, Julien Tabareau³, Jean-Claude Sirard³, José A Chabalgoity¹

Affiliations

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.

PMID: 27546231
DOI: 10.2217/fmb-2016-0045

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.

Keywords: Streptococcus pneumoniae; TLR5; antimicrobial; flagellin; immunotherapy; neutrophils; pneumonia; sublingual.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Sublingual
Animals
Bacterial Proteins / administration & dosage
Bacterial Proteins / chemistry
Bacterial Proteins / genetics
Bacterial Proteins / immunology*
Bacterial Vaccines / administration & dosage
Bacterial Vaccines / chemistry
Bacterial Vaccines / genetics
Bacterial Vaccines / immunology
CARD Signaling Adaptor Proteins / genetics
CARD Signaling Adaptor Proteins / immunology*
Calcium-Binding Proteins / genetics
Calcium-Binding Proteins / immunology*
Female
Flagellin / administration & dosage
Flagellin / chemistry
Flagellin / genetics
Flagellin / immunology*
Humans
Lung / immunology
Lung / microbiology
Mice
Mice, Inbred BALB C
Neutrophils / immunology
Pneumonia, Pneumococcal / genetics
Pneumonia, Pneumococcal / immunology*
Pneumonia, Pneumococcal / microbiology
Pneumonia, Pneumococcal / prevention & control*
Protein Domains
Streptococcus pneumoniae / genetics
Streptococcus pneumoniae / immunology*
Toll-Like Receptor 5 / genetics
Toll-Like Receptor 5 / immunology*

Substances

Bacterial Proteins
Bacterial Vaccines
CARD Signaling Adaptor Proteins
Calcium-Binding Proteins
NLRC4 protein, human
TLR5 protein, human
Toll-Like Receptor 5
Flagellin