ABSTRACT
Pneumonia caused by the intracellular bacterium Rhodococcus equi is an important cause of disease and death in immunocompromised hosts, especially foals. Antibiotics are the standard of care for treating R. equi pneumonia in foals, and adjunctive therapies are needed. We tested whether nebulization with TLR agonists (PUL-042) in foals would improve innate immunity and reduce the severity and duration of pneumonia following R. equi infection. Neonatal foals (n = 48) were nebulized with either PUL-042 or vehicle, and their lung cells infected ex vivo. PUL-042 increased inflammatory cytokines in BAL fluid and alveolar macrophages after ex vivo infection with R. equi. Then, the in vivo effects of PUL-042 on clinical signs of pneumonia were examined in 22 additional foals after intrabronchial challenge with R. equi. Foals infected and nebulized with PUL-042 or vehicle alone had a shorter duration of clinical signs of pneumonia and smaller pulmonary lesions when compared to non-nebulized foals. Our results demonstrate that host-directed therapy can enhance neonatal immune responses against respiratory pathogens and reduce the duration and severity of R. equi pneumonia.
Subject(s)
Actinomycetales Infections , Horse Diseases , Horses , Immunity, Innate/drug effects , Lipopeptides/pharmacology , Oligodeoxyribonucleotides/pharmacology , Pneumonia, Bacterial , Rhodococcus equi/immunology , Toll-Like Receptor 2/agonists , Toll-Like Receptor 6/agonists , Toll-Like Receptor 9/agonists , Actinomycetales Infections/drug therapy , Actinomycetales Infections/immunology , Actinomycetales Infections/pathology , Actinomycetales Infections/veterinary , Animals , Horse Diseases/drug therapy , Horse Diseases/immunology , Horse Diseases/pathology , Horses/immunology , Horses/microbiology , Macrophages, Alveolar/immunology , Macrophages, Alveolar/pathology , Pneumonia, Bacterial/drug therapy , Pneumonia, Bacterial/immunology , Pneumonia, Bacterial/pathology , Pneumonia, Bacterial/veterinary , Severity of Illness IndexABSTRACT
A patient with hepatitis C infection and hepatocellular carcinoma developed significant hyperbilirubinemia and acute kidney injury after initiation of a simeprevir and sofosbuvir regimen.
