title: 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.
authors.affiliation: Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, United States.
authors.forename: Londa J
authors.initials: LJ
authors.lastname: Berghaus
authors.affiliation: Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, United States. Electronic address: gigueres@uga.edu.
authors.forename: Steeve
authors.initials: S
authors.lastname: Giguère
authors.affiliation: Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, United States.
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Sturgill
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology; D006736:Horses / Q000276:immunology*; D008264:Macrophages / Q000145:classification* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016929:Rhodococcus equi / Q000502:physiology*
chemical_list: D016207:Cytokines; D012333:RNA, Messenger
keywords: Cytokines; Foal; Macrophage; Pneumonia; Rhodococcus equi