A toll-like receptor 5 agonist improves the efficacy of antibiotics in the treatment of primary and influenza-associated pneumococcal mouse infections
| Autor: | Natalia Muñoz-Wolf, Frédéric Wallet, Rémi Porte, José A. Chabalgoity, François Trottein, Christophe Paget, Julien Tabareau, Anne-France Georgel, Christophe Carnoy, Delphine Fougeron, Jean-Claude Sirard |
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| Přispěvatelé: | Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Universidad de la República [Montevideo] (UCUR), Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), Service de Bactériologie, Virologie, Hygiène [CHU Limoges], CHU Limoges, This work was funded by INSERM, CNRS, Institut Pasteur de Lille, and Université de Lille (to R.P., D.F., J.T., A.-F.G., C.P., F.T., C.C., and J.-C.S), Région Nord Pas de Calais (Ph.D. fellowship), and Inserm-Transfert (CoPoC grant 'Innatebiotic')., We thank Delphine Cayet and Daphnée Soulard for technical assistance in the production and quality control of recombinant proteins and Isabelle Wolowczuk, Sandra Weller, and Philippe Gosset for critical reading of the manuscript., Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Universidad de la República [Montevideo] (UDELAR), Université catholique de Lille (UCL), Sirard, Jean-Claude |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Antibiotics
MESH: Pneumococcal Infections/drug therapy medicine.disease_cause MESH: Flagellin/therapeutic use Mice 0302 clinical medicine [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases MESH: Trimethoprim Sulfamethoxazole Drug Combination/therapeutic use MESH: Toll-Like Receptor 5/agonists Pharmacology (medical) MESH: Animals MESH: Streptococcus pneumoniae/pathogenicity MESH: Immunity Innate/drug effects 0303 health sciences Mice Inbred BALB C 3. Good health Anti-Bacterial Agents Infectious Diseases Streptococcus pneumoniae Neutrophil Infiltration [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases Female medicine.drug medicine.drug_class MESH: Mice Inbred BALB C Biology Pneumococcal Infections Microbiology 03 medical and health sciences Immunity MESH: Streptococcus pneumoniae/drug effects Trimethoprim Sulfamethoxazole Drug Combination medicine Animals MESH: Neutrophil Infiltration/drug effects Experimental Therapeutics MESH: Amoxicillin/therapeutic use MESH: Mice 030304 developmental biology MESH: Anti-Bacterial Agents/therapeutic use Pharmacology Amoxicillin medicine.disease Immunity Innate Pneumonia Toll-Like Receptor 5 TLR5 Immunology biology.protein Nasal administration MESH: Female Flagellin 030215 immunology |
| Zdroj: | Antimicrobial Agents and Chemotherapy Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2015, 59 (10), pp.6064-6072. ⟨10.1128/AAC.01210-15⟩ Antimicrobial Agents and Chemotherapy, 2015, 59 (10), pp.6064-6072. ⟨10.1128/AAC.01210-15⟩ |
| ISSN: | 0066-4804 1098-6596 |
| Popis: | Prophylactic intranasal administration of the Toll-like receptor 5 (TLR5) agonist flagellin protects mice against respiratory pathogenic bacteria. We hypothesized that TLR5-mediated stimulation of lung immunity might improve the therapeutic index of antibiotics for the treatment of Streptococcus pneumoniae respiratory infections in mice. Intranasal administration of flagellin was combined with either oral administration of amoxicillin or intraperitoneal injection of trimethoprim-sulfamethoxazole to treat S. pneumoniae -infected animals. Compared with standalone treatments, the combination of antibiotic and flagellin resulted in a lower bacterial load in the lungs and greater protection against S. pneumoniae dissemination and was associated with an early increase in neutrophil infiltration in the airways. The antibiotic-flagellin combination treatment was, however, not associated with any exacerbation of inflammation. Moreover, combination treatment was more efficacious than standalone antibiotic treatments in the context of post-influenza virus pneumococcal infection. Lastly, TLR5 signaling was shown to be mandatory for the efficacy of the combined antibacterial therapy. This report is the first to show that combining antibiotic treatment with the stimulation of mucosal innate immunity is a potent antibacterial strategy against pneumonia. |
| Databáze: | OpenAIRE |
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