Host-directed therapy in foals can enhance functional innate immunity and reduce severity of Rhodococcus equi pneumonia

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 nebu...

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Autores principales:	Angela I. Bordin, Noah D. Cohen, Steve Giguère, Jocelyne M. Bray, Londa J. Berghaus, Brenton Scott, Rena Johnson, Magnus Hook
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2eca7bb4bc0245208a68a762cbf5daa9
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spelling	oai:doaj.org-article:2eca7bb4bc0245208a68a762cbf5daa92021-12-02T13:57:49ZHost-directed therapy in foals can enhance functional innate immunity and reduce severity of Rhodococcus equi pneumonia10.1038/s41598-021-82049-y2045-2322https://doaj.org/article/2eca7bb4bc0245208a68a762cbf5daa92021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82049-yhttps://doaj.org/toc/2045-2322Abstract 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.Angela I. BordinNoah D. CohenSteve GiguèreJocelyne M. BrayLonda J. BerghausBrenton ScottRena JohnsonMagnus HookNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Angela I. Bordin Noah D. Cohen Steve Giguère Jocelyne M. Bray Londa J. Berghaus Brenton Scott Rena Johnson Magnus Hook Host-directed therapy in foals can enhance functional innate immunity and reduce severity of Rhodococcus equi pneumonia
description	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.
format	article
author	Angela I. Bordin Noah D. Cohen Steve Giguère Jocelyne M. Bray Londa J. Berghaus Brenton Scott Rena Johnson Magnus Hook
author_facet	Angela I. Bordin Noah D. Cohen Steve Giguère Jocelyne M. Bray Londa J. Berghaus Brenton Scott Rena Johnson Magnus Hook
author_sort	Angela I. Bordin
title	Host-directed therapy in foals can enhance functional innate immunity and reduce severity of Rhodococcus equi pneumonia
title_short	Host-directed therapy in foals can enhance functional innate immunity and reduce severity of Rhodococcus equi pneumonia
title_full	Host-directed therapy in foals can enhance functional innate immunity and reduce severity of Rhodococcus equi pneumonia
title_fullStr	Host-directed therapy in foals can enhance functional innate immunity and reduce severity of Rhodococcus equi pneumonia
title_full_unstemmed	Host-directed therapy in foals can enhance functional innate immunity and reduce severity of Rhodococcus equi pneumonia
title_sort	host-directed therapy in foals can enhance functional innate immunity and reduce severity of rhodococcus equi pneumonia
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2eca7bb4bc0245208a68a762cbf5daa9
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Host-directed therapy in foals can enhance functional innate immunity and reduce severity of Rhodococcus equi pneumonia

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