Author:
Bordin Angela I.,Cohen Noah D.,Giguère Steve,Bray Jocelyne M.,Berghaus Londa J.,Scott Brenton,Johnson Rena,Hook Magnus
Abstract
AbstractPneumonia 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.
Funder
Grayson-Jockey Club Research Foundation
Morris Animal Foundation
Link Equine Research Endowment
Publisher
Springer Science and Business Media LLC
Reference66 articles.
1. Takai, S. et al. Correlation of in vitro properties of Rhodococcus (Corynebacterium) equi with virulence for mice. Microbiol. Immunol. 29(12), 1175–1184 (1985).
2. Horowitz, M. L. et al. Application of Sartwell’s model (lognormal distribution of incubation periods) to age at onset and age at death of foals with Rhodococcus equi pneumonia as evidence of perinatal infection. J. Vet. Intern. Med. 15(3), 171–175 (2001).
3. Sanz, M. et al. The effect of bacterial dose and foal age at challenge on Rhodococcus equi infection. Vet. Microbiol. 167(3–4), 623–631 (2013).
4. Liu, T. et al. Basal and stimulus-induced cytokine expression is selectively impaired in peripheral blood mononuclear cells of newborn foals. Vaccine 27(5), 674–683 (2009).
5. Flaminio, M. J. et al. Characterization of peripheral blood and pulmonary leukocyte function in healthy foals. Vet. Immunol. Immunopathol. 73(3–4), 267–285 (2000).
Cited by
11 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献