Abstract
Free-living amoebae of the genus Acanthamoeba can cause severe and chronic infections in humans, mainly localized in immune privileged sites, such as the brain and the eye. Monocytes/macrophages are thought to be involved in Acanthamoeba infections, but little is known about how these facultative parasites influence their functions. The aim of this work was to investigate the effects of Acanthamoeba on human monocytes/macrophages during the early phase of infection. Here, THP-1 cells, primary human monocytes isolated from peripheral blood, and human monocyte-derived macrophages were either coincubated with trophozoites of a clinical isolate of Acanthamoeba (genotype T4) or stimulated with amoeba-derived cell-free conditioned medium. Production of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin-6 [IL-6], and IL-12), anti-inflammatory cytokine (IL-10), and chemokine (IL-8) was evaluated at specific hours poststimulation (ranging from 1.5 h to 23 h). We showed that both Acanthamoeba trophozoites and soluble amoebic products induce an early anti-inflammatory monocyte-macrophage phenotype, characterized by significant production of IL-10; furthermore, challenge with either trophozoites or their soluble metabolites stimulate both proinflammatory cytokines and chemokine production, suggesting that this protozoan infection results from the early induction of coexisting, opposed immune responses. Results reported in this paper confirm that the production of proinflammatory cytokines and chemokines by monocytes and macrophages can play a role in the development of the inflammatory response during Acanthamoeba infections. Furthermore, we demonstrate for the first time that Acanthamoeba stimulates IL-10 production in human innate immune cells, which might both promote the immune evasion of Acanthamoeba and limit the induced inflammatory response.
Highlights
Ubiquitous amoebae of the genus Acanthamoeba are amphizoic protozoa with the ability to exist both as free-living organisms in nature and as parasites within host tissues [1]
Coincubation of THP-1 with trophozoites caused a significant increase of TNF-␣, which peaked at 4 h (130.747 Ϯ 8.689 pg/ml, n ϭ 5, P Ͻ 0.0001) and decreased drastically (Fig. 1A)
Our study indicates that human monocytes and human macrophages can recognize and respond to Acanthamoeba trophozoites as well as to amoebic soluble compounds, releasing cytokines and chemokines with different kinetics and intensity
Summary
Ubiquitous amoebae of the genus Acanthamoeba are amphizoic protozoa with the ability to exist both as free-living organisms in nature and as parasites within host tissues [1]. Numerous reports indicate that several species of Acanthamoeba can infect humans, producing severe ocular disease and almost invariably fatal neurological disease [2,3,4,5,6,7]. GAE has been reported in healthy individuals [3, 8,9,10,11] In some cases, these apparently immunocompetent GAE patients had a history of exposed skin lesions, chronic sinusitis, rhinitis, or pneumonia [12], suggesting that Acanthamoeba can reach the central nervous system through three main portals of entry: skin lesions, the respiratory tract, and the olfactory neuroepithelium. AK is mainly associated with use of contact lenses (CLs) This is for a number of reasons, including the ability of CLs to cause microcorneal trauma, and their inappropriate use, maintenance, and cleaning can facilitate their contamination with Acanthamoeba [13]. Very little is known about the biochemical mechanisms that occur in human monocytes upon exposure to Acanthamoeba trophozoites or their products
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