Effects of priming with cytokines on intracellular survival and replication of Rhodococcus equi in equine macrophages

Abstract

Rhodococcus equi is a common cause of pneumonia in foals and an opportunistic pathogen in immunosuppressed people. The ability of R. equi to survive and replicate in macrophages is the basis of its pathogenicity. Limited knowledge about the role of cytokines in host defense against R. equi comes from studies in mice and the role of cytokines in intracellular survival of R. equi in equine macrophages is unknown. The objectives of this study were to determine the effect of priming with interferon (IFN)-γ, interleukin (IL)-1β, IL-4, IL-6, IL-10, or tumor necrosis factor (TNF)-α at various concentrations on intracellular survival of virulent R. equi in equine monocyte-derived macrophages (MDM), and to determine the effects of various combinations of the same cytokines on intracellular survival of R. equi. MDM from 10 adult horses were primed with recombinant equine cytokines at doubling concentrations ranging from 25 to 200 ng/mL prior to infection with virulent R. equi. Priming with IFN-γ, TNF-α, or IL-6 significantly decreased intracellular replication of R. equi compared to unprimed monolayers. In contrast, priming with IL-10 or IL-1β significantly increased intracellular replication of R. equi. Pairwise combinations of the cytokines listed above did not results in synergism or antagonism. This study demonstrated that IFN-γ, TNF-α, or IL-6 improved equine MDM function against R. equi whereas IL-1β or IL-10 were detrimental.