The impact of age on vitamin D receptor expression, vitamin D metabolism and cytokine production in ex vivo Rhodococcus equi infection of equine alveolar macrophages.
Abstract: Rhodococcus equi (R. equi), a pneumonia-causing intracellular bacterium, results in significant morbidity and mortality in young foals, while healthy adult horses rarely develop disease. Survival and replication within alveolar macrophages (AMφ) are the hallmarks of R. equi's pathogenicity. The vitamin D receptor (VDR) and its ligand, the active vitamin D metabolite 1,25(OH)2D, are important in immune responses to intracellular bacteria. The vitamin D/VDR pathway regulates the downstream production of cytokines in infected human AMφ. The immunomodulatory role of the vitamin D/VDR pathway in equine leukocytes is unknown. The objective of the current study was to determine the impact of R. equi infection and age on synthesis of 1,25(OH)2D, VDR expression, and cytokine production in an ex vivo model of R. equi infection in equine AMφ. AMφ were collected from ten healthy foals at 2-, 4- and 8-weeks old and from nine healthy adult horses once via bronchoalveolar lavage. AMφ were mock infected (CONTROL) or infected with a virulent laboratory strain of R. equi for 7 days (INFECTED). VDR expression was determined via RT-qPCR from cell lysates. 1,25(OH)2D and cytokines were measured in cell supernatant by immunoassays. VDR expression was impacted by age (P = 0.001) with higher expression in AMφ from 8-week-old foals than from 2-week-old foals and adults. There was no significant effect of infection in foal AMφ, but in adults, relative VDR expression was significantly lower in INFECTED AMφ compared to CONTROL AMφ (P = 0.002). There was no effect of age or infection on 1,25(OH)2D concentration (P > 0.37). Mean TNFα production was significantly higher from INFECTED compared to CONTROL AMφ from 4- and 8-week-old foals and adults (P < 0.005). Mean IFNγ production was significantly higher from AMφ from foals at 8-weeks-old compared to 2-weeks-old (P = 0.013) and higher from INFECTED AMφ than from CONTROL AMφ in foals at 4-weeks-old and in adults (P < 0.027). The proportion of samples producing IL-1β and IL-10 was also significantly higher from INFECTED compared to CONTROL AMφ isolated from 4-week-old foals (P < 0.008). Similarly, in adult samples, IL-17 was produced from a greater proportion of INFECTED compared to CONTROL samples (P = 0.031). These data document age-associated changes in VDR expression and cytokine production in equine AMφ in response to R. equi infection. This preliminary investigation supports the need for further research to fully elucidate if the vitamin D pathway has an immunomodulatory role in the horse.
Copyright © 2024 Elsevier B.V. All rights reserved.
Publication Date: 2024-01-02 PubMed ID: 38181474DOI: 10.1016/j.vetimm.2023.110707Google Scholar: Lookup
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Summary
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The abstract discusses a study exploring the role of vitamin D and its receptor (VDR) in the immune response of horses to the bacterium, Rhodococcus equi, which causes pneumonia. The study found that the age of the horse influences VDR expression and immune response, contributing to our understanding of why young foals are more susceptible to infection than healthy adult horses.
Objective and Methodology
- The primary purpose of the study was to examine the effect of Rhodococcus equi infection and age on the production of active vitamin D, VDR expression, and cytokine production in horses’ alveolar macrophages (AMφ), immune cells in the lungs.
- Researchers collected AMφ from 10 foals (at 2, 4, and 8 weeks old) and nine adult horses using bronchoalveolar lavage, a method for sampling cells from the lower respiratory tract.
- These AMφ samples were either infected with a strain of R. equi for seven days or left uninfected as a control.
- VDR expression was determined by RT-qPCR (a technique that quantifies specific mRNA levels) from cell extracts, while the active form of vitamin D and cytokines were measured in the cell supernatant using immunoassays.
Key Findings
- The study found that age affected VDR expression, showing higher expression in AMφ from 8-week-old foals than from 2-week-old foals and adults.
- In adults, VDR expression was significantly lower in infected AMφ compared to uninfected control cells.
- However, the concentration of active vitamin D wasn’t influenced by age or infection status.
- Production of inflammatory cytokines such as TNFα and IFNγ were significantly higher in infected AMφ. This was especially observed in 4 and 8-week-old foals and adults.
- In 8-week-old foals, the production of IFNγ, a cytokine crucial for innate and adaptive immunity, was significantly higher when compared to 2-week-olds.
- The proportion of samples producing cytokines IL-1β and IL-10 was significantly higher in infected compared to uninfected control cells from 4-week-old foals. Similarly, a greater proportion of infected adult samples produced the cytokine IL-17 compared to control samples.
Implications and Conclusions
- The study reveals age-associated changes in VDR expression and cytokine production in the immune response of horses to R. equi infection.
- This suggests that the vitamin D/VDR pathway could have a regulatory role in the immune response of horses, particularly in the context of age and susceptibility to R. equi.
- The researchers recommend further studies to clarify the potential immunomodulatory function of the vitamin D pathway in horses and inform the development of improved treatments for R. equi infections in foals.
Cite This Article
APA
Berghaus LJ, Cathcart J, Berghaus RD, Ryan C, Toribio RE, Hart KA.
(2024).
The impact of age on vitamin D receptor expression, vitamin D metabolism and cytokine production in ex vivo Rhodococcus equi infection of equine alveolar macrophages.
Vet Immunol Immunopathol, 268, 110707.
https://doi.org/10.1016/j.vetimm.2023.110707 Publication
Researcher Affiliations
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens GA 30605, USA. Electronic address: ljberg@uga.edu.
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens GA 30605, USA.
- Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens GA 30605, USA.
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens GA 30605, USA.
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus OH 43210, USA.
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens GA 30605, USA.
MeSH Terms
- Animals
- Actinomycetales Infections / veterinary
- Cytokines / metabolism
- Horse Diseases
- Horses
- Macrophages, Alveolar / metabolism
- Receptors, Calcitriol
- Rhodococcus equi
- Vitamin D
Conflict of Interest Statement
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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