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Effects of age and macrophage lineage on intracellular survival and cytokine induction after infection with Rhodococcus equi.
Abstract: Rhodococcus equi, a facultative intracellular pathogen of macrophages, causes life-threatening pneumonia in foals and in people with underlying immune deficiencies. As a basis for this study, we hypothesized that macrophage lineage and age would affect intracellular survival of R. equi and cytokine induction after infection. Monocyte-derived and bronchoalveolar macrophages from 10 adult horses and from 10 foals (sampled at 1-3 days, 2 weeks, 1 month, 3 months, and 5 months of age) were infected ex vivo with virulent R. equi. Intracellular R. equi were quantified and mRNA expression of IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12 p40, IL-18, IFN-γ, and TNF-α was measured. Intracellular replication of R. equi was significantly (P<0.001) greater in bronchoalveolar than in monocyte-derived macrophages, regardless of age. Regardless of the macrophage lineage, replication of R. equi was significantly (P=0.002) higher in 3-month-old foals than in 3-day old foals, 2-week-old foals, 1-month-old foals, and adult horses. Expression of IL-4 mRNA was significantly higher in monocyte-derived macrophages whereas expression of IL-6, IL-18, and TNF-α was significantly higher in bronchoalveolar macrophages. Induction of IL-1β, IL-10, IL-12 p40, and IL-8 mRNA in bronchoalveolar macrophages of 1-3-day old foals was significantly higher than in older foals or adult horses. Preferential intracellular survival of R. equi in bronchoalveolar macrophages of juvenile horses may play a role in the pulmonary tropism of the pathogen and in the window of age susceptibility to infection.
Copyright © 2014 Elsevier B.V. All rights reserved.
Publication Date: 2014-03-29 PubMed ID: 24736188DOI: 10.1016/j.vetimm.2014.03.010Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
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.
This research studies how age and type of immune cell (macrophage lineage) influence the survival of a pathogen, Rhodococcus equi, and its ability to stimulate an immune response (cytokine induction). Rhodococcus equi causes serious lung infections and is dangerous for young horses (foals) and immunocompromised individuals.
Background and Aims
- The purpose of this study was to understand how the type of immune cell (macrophage lineage – monocyte-derived and bronchoalveolar) and the age of the host (horse) affects the survival and subsequent replication of Rhodococcus equi, a harmful pathogen.
- The researchers hypothesized that both the specific type of macrophage and the age of the host would significantly influence the intracellular survival of Rhodococcus equi and the level of immune response after infection.
Methods
- The study used monocyte-derived and bronchoalveolar macrophages taken from 10 adult horses and 10 foals of varying ages (1-3 days, 2 weeks, 1 month, 3 months, and 5 months).
- These macrophages were infected ex vivo (outside the body) with virulent Rhodococcus equi.
- The researchers then quantified the Rhodococcus equi within the cells and measured the mRNA expression of various cytokines – proteins that regulate immune response.
Results
- Rhodococcus equi replication was significantly higher in bronchoalveolar macrophages than in monocyte-derived macrophages, regardless of the age of the horse.
- Within any cell type, the replication of R. equi was significantly higher in 3-month-old foals compared to those aged 3-days, 2-weeks, 1-month, and to adult horses.
- The expression of certain cytokines was significantly higher in specific macrophages: IL-4 in monocyte-derived macrophages and IL-6, IL-18, and TNF-α in bronchoalveolar macrophages.
- There was greater induction of IL-1β, IL-10, IL-12 p40, and IL-8 mRNA in bronchoalveolar macrophages from 1-3-day old foals than in older foals or adult horses.
Conclusion and Implications
- Rhodococcus equi infection and subsequent intracellular survival was affected by both the age of the host and the lineage of macrophages, confirming the study hypothesis.
- The fact that Rhodococcus equi was found to preferentially survive within bronchoalveolar macrophages of young horses suggests a potential reason for the pathogen’s tendency to infect lungs and a reason behind the higher susceptibility of young horses to the infection.
Cite This Article
APA
Berghaus LJ, Giguère S, Sturgill TL.
(2014).
Effects of age and macrophage lineage on intracellular survival and cytokine induction after infection with Rhodococcus equi.
Vet Immunol Immunopathol, 160(1-2), 41-50.
https://doi.org/10.1016/j.vetimm.2014.03.010 Publication
Researcher Affiliations
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, United States.
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, United States. Electronic address: gigueres@uga.edu.
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, United States.
MeSH Terms
- Aging / immunology
- Animals
- Cells, Cultured
- Cytokines / genetics
- Cytokines / metabolism
- Gene Expression Regulation / immunology
- Horses / immunology
- Macrophages / classification
- Macrophages / immunology
- Macrophages / metabolism
- Macrophages / microbiology
- RNA, Messenger / genetics
- RNA, Messenger / metabolism
- Rhodococcus equi / physiology
Citations
This article has been cited 14 times.- Rivolta AA, Bujold AR, Wilmarth PA, Phinney BS, Navelski JP, Horohov DW, Sanz MG. Comparison of the broncoalveolar lavage fluid proteomics between foals and adult horses. PLoS One 2023;18(9):e0290778.
- Kang H, Lee GKC, Bienzle D, Arroyo LG, Sears W, Lillie BN, Beeler-Marfisi J. Equine alveolar macrophages and monocyte-derived macrophages respond differently to an inflammatory stimulus. PLoS One 2023;18(3):e0282738.
- Rivolta AA, Pittman DC, Kappes AJ, Stancil RK, Kogan C, Sanz MG. The type of anticoagulant used for plasma collection affects in vitro Rhodococcus equi assays. BMC Res Notes 2022 Feb 14;15(1):50.
- Bordin AI, Cohen ND, Giguère S, Bray JM, Berghaus LJ, Scott B, Johnson R, Hook M. Host-directed therapy in foals can enhance functional innate immunity and reduce severity of Rhodococcus equi pneumonia. Sci Rep 2021 Jan 28;11(1):2483.
- Harvey AB, Bordin AI, Rocha JN, Bray JM, Cohen ND. Opsonization but not pretreatment of equine macrophages with hyperimmune plasma nonspecifically enhances phagocytosis and intracellular killing of Rhodococcus equi. J Vet Intern Med 2021 Jan;35(1):590-596.
- Bujold AR, Lani NR, Sanz MG. Strain-to-strain variation of Rhodococcus equi growth and biofilm formation in vitro. BMC Res Notes 2019 Aug 19;12(1):519.
- Willingham-Lane JM, Berghaus LJ, Berghaus RD, Hart KA, Giguère S. Effect of Macrolide and Rifampin Resistance on Fitness of Rhodococcus equi during Intramacrophage Replication and In Vivo. Infect Immun 2019 Oct;87(10).
- Liu X, Ma Q, Sun X, Lu M, Ehsan M, Hasan MW, Xu L, Yan R, Song X, Li X. Effects of Recombinant Toxoplasma gondii Citrate Synthase I on the Cellular Functions of Murine Macrophages In vitro. Front Microbiol 2017;8:1376.
- Giles C, Ndi O, Barton MD, Vanniasinkam T. An Adenoviral Vector Based Vaccine for Rhodococcus equi. PLoS One 2016;11(3):e0152149.
- Villalba-Orero M, Gómez CA, Valero-Gónzalez M, Venegas N, Criado G, Martín-Cuervo M. Blood parameters in neonatal foal and colostrum quality as possible early markers for increased risk of developing Rhodococcus equi pneumonia. Front Vet Sci 2025;12:1654052.
- Berghaus LJ, Venner M, Helbig H, Hildebrandt D, Hart K. The potential value of cytokine, cortisol and vitamin D profiles in foals from birth to weaning for respiratory disease prediction on a farm endemic for Rhodococcus equi pneumonia. Equine Vet J 2026 Mar;58(2):359-371.
- Huguet A-S, Gourbeyre O, Bousquet-Mélou A, Ferran AA, Lallemand EA. Reassessment of extracellular and intracellular activity of macrolides, rifampicin, and doxycycline against Rhodococcus equi based on bacterial counts and microscopy. Microbiol Spectr 2025 Sep 2;13(9):e0120525.
- da Silveira BP, Cohen ND, Lawhon SD, Watson RO, Bordin AI. Protective immune response against Rhodococcus equi: An innate immunity-focused review. Equine Vet J 2025 May;57(3):563-586.
- da Silveira BP, Barhoumi R, Bray JM, Cole-Pfeiffer HM, Mabry CJ, Burghardt RC, Cohen ND, Bordin AI. Impact of surface receptors TLR2, CR3, and FcγRIII on Rhodococcus equi phagocytosis and intracellular survival in macrophages. Infect Immun 2024 Jan 16;92(1):e0038323.
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