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Scientific reports2021; 11(1); 2483; doi: 10.1038/s41598-021-82049-y

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 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.
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Publication Date: 2021-01-28 PubMed ID: 33510265PubMed Central: PMC7844249DOI: 10.1038/s41598-021-82049-yGoogle Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study explores using host-directed therapy, specifically nebulization with TLR agonists (PUL-042), to improve the immunity of foals against pneumonia caused by Rhodococcus equi and reduce the severity of the disease. Trials showed that PUL-042 increased inflammatory cytokines, and foals treated with such had less severe and shorter-lived symptoms of pneumonia.

Study Overview

  • This research primarily aims to find effective remedies for pneumonia in foals, especially pneumonia caused by the intracellular bacterium Rhodococcus equi, which is notably harmful for those with compromised immune systems.
  • Typically, antibiotics are used to cure R. equi pneumonia but additional treatments are needed. This study tests whether PUL-042, a Toll-Like Receptor (TLR) agonist, delivered through nebulization can not only boost the foals’ innate immunity but lessen the severity and duration of the pneumonia following an R. equi infection.

Methodology and Findings

  • The study involved a total of 70 foals.
  • 48 neonatal foals were treated with a nebulizer filled with either PUL-042 or a control solution, and then their lung cells were infected in a laboratory setting.
  • The results showed that PUL-042 increased the presence of inflammatory cytokines in the bronchoalveolar lavage (BAL) fluid and the alveolar macrophages after ex vivo infection with R. equi. This signifies a higher immune response in the organisms.
  • To further verify the results, an in vivo trial was conducted on 22 more foals. They were intrabronchially challenged with R. equi, after which their pneumonia signs were observed.
  • Those infected and treated with PUL-042 or just the control solution had less severe symptoms of pneumonia and their pulmonary lesions were smaller in comparison to the foals who were not nebulized.

Conclusions

  • This study demonstrated that host-directed therapy can ameliorate neonatal immune responses against respiratory pathogens, resulting in less severe and shorter durations of R. equi pneumonia.
  • As a recommendation for practice, it suggests that nebulization with TLR agonist PUL-042 can potentially serve as an adjunctive therapy alongside antibiotics for foals afflicted by R. equi pneumonia.

Cite This Article

APA
Bordin AI, Cohen ND, Giguère S, Bray JM, Berghaus LJ, Scott B, Johnson R, Hook M. (2021). Host-directed therapy in foals can enhance functional innate immunity and reduce severity of Rhodococcus equi pneumonia. Sci Rep, 11(1), 2483. https://doi.org/10.1038/s41598-021-82049-y

Publication

Scientific reports
ISSN: 2045-2322
NlmUniqueID: 101563288
Country: England
Language: English
Volume: 11
Issue: 1
Pages: 2483

Researcher Affiliations

Bordin, Angela I
  • Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, USA. abordin@cvm.tamu.edu.
Cohen, Noah D
  • Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, USA.
Giguère, Steve
  • Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
Bray, Jocelyne M
  • Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, USA.
Berghaus, Londa J
  • Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
Scott, Brenton
  • Pulmotect, Inc., Houston, TX, USA.
Johnson, Rena
  • Pulmotect, Inc., Houston, TX, USA.
Hook, Magnus
  • Institute of Biosciences and Technology, Center for Infectious and Inflammatory Diseases, Texas A&M University, Houston, TX, USA.

MeSH Terms

  • 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
  • Immunity, Innate / drug effects
  • Lipopeptides / pharmacology
  • Macrophages, Alveolar / immunology
  • Macrophages, Alveolar / pathology
  • Oligodeoxyribonucleotides / pharmacology
  • Pneumonia, Bacterial / drug therapy
  • Pneumonia, Bacterial / immunology
  • Pneumonia, Bacterial / pathology
  • Pneumonia, Bacterial / veterinary
  • Rhodococcus equi / immunology
  • Severity of Illness Index
  • Toll-Like Receptor 2 / agonists
  • Toll-Like Receptor 6 / agonists
  • Toll-Like Receptor 9 / agonists

Conflict of Interest Statement

Dr. Hook has received compensation as a member of the scientific advisory board of Pulmotect, Inc. and owns stock options in the company. Drs. Scott and Johnson are employees of Pulmotect, Inc. and own stock options in the company. The other authors declare no competing interests.

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