Title :

The Biosynthetic Monophosphoryl Lipid A Enhances the Therapeutic Outcome of Antibiotic Therapy in Pneumococcal Pneumonia.

Author(s) :

Casilag, Fiordiligie [Auteur]
Matarazzo, Laura [Auteur]
Franck, Sebastian [Auteur]
Figeac, Martin [Auteur]
Michelet, Robin [Auteur]
Kloft, Charlotte [Auteur]
Carnoy, Christophe [Auteur]
Sirard, Jean-Claude [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]

Journal title :

Acs Infectious Diseases

Pages :

2164-2175

Publisher :

American Chemical Society

Publication date :

2021-08-13

English keyword(s) :

Streptococcus pneumoniae
Toll-like receptor
adjunct therapy
amoxicillin
bacterial pneumonia

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Alternative treatment strategies against bacterial infections are required to decrease the use of antibiotics. This study tested the hypothesis that stimulation of the innate immune receptor Toll-like receptor 4 can be ...
Show more >Alternative treatment strategies against bacterial infections are required to decrease the use of antibiotics. This study tested the hypothesis that stimulation of the innate immune receptor Toll-like receptor 4 can be combined with antibiotics to improve the treatment of invasive pneumonia. The efficacy of the biosynthetic monophosphoryl lipid A (MPLA), a clinically approved Toll-like receptor 4 activator, was tested in a mouse model of Streptococcus pneumoniae respiratory infection. Interestingly, administration of amoxicillin or MPLA decreased 400- to 11 000-fold the bacterial load in the lungs and spleen but did not enhance survival compared to mock treatment. The single administration of a combination of MPLA and amoxicillin further reduced 10- to 18-fold the bacterial colonization and invasion and significantly improved protection against lethal disease. The combined administration of MPLA and amoxicillin in a context of infection was associated with transient increase of the serum concentrations of amoxicillin and pro-inflammatory cytokines and chemokines as well as the expression of immune genes in lung tissue. Remarkably, the systemic and lung immune activation extended beyond amoxicillin elimination, suggesting a two-step and cooperative anti-infective effect, i.e., rapid antibiotic-mediated alteration of bacteria and a long-lasting impact through mucosal and systemic immunity. Our proof-of-concept study demonstrated for the first time that boosting Toll-like receptor 4 signaling can synergize with antibiotics in order to increase the efficacy of therapy of bacterial pneumonia, thereby in fine reducing the dose or regimen of antibiotics.Show less >

Language :

Anglais

Popular science :

Non

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL