Characteristic pro-inflammatory cytokines and host defence cathelicidin peptide produced by human monocyte-derived macrophages infected withNeospora caninum

Abstract

AbstractNeospora caninumis a coccidian intracellular protozoan capable of infecting a wide range of mammals, although severe disease is mostly reported in dogs and cattle. Innate defences triggered by monocytes/macrophages are key in the pathogenesis of neosporosis, as these cells are first-line defenders against intracellular infections. The aim of this study was to characterize infection and innate responses in macrophages infected withN. caninumusing a well-known cell model to study macrophage functions (human monocyte THP-1 cells). Intracellular invasion of live tachyzoites occurred as fast as 4 h (confirmed with immunofluorescence microscopy usingN. caninum-specific antibodies). Macrophages infected byN. caninumhad increased expression of pro-inflammatory cytokines (TNFα, IL-1β, IL-8, IFNγ). Interestingly,N. caninuminduced expression of host-defence peptides (cathelicidins), a mechanism of defence never reported forN. caninuminfection in macrophages. The expression of cytokines and cathelicidins in macrophages invaded byN. caninumwas mediated by mitogen-activated protein kinase (MEK 1/2). Secretion of such innate factors fromN. caninum-infected macrophages reduced parasite internalization and promoted the secretion of pro-inflammatory cytokines in naïve macrophages. We concluded that rapid invasion of macrophages byN. caninumtriggered protective innate defence mechanisms against intracellular pathogens.