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The interaction of Acanthamoeba spp. with activated macrophages and with macrophage cell lines
1Department of Microbiology and Immunology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0678, USA. fmcabral@gems.vcu.edu
Abstract:
Acanthamoeba spp. are free-living amebae associated with amebic keratitis and chronic granulomatous amebic encephalitis. The present studies were undertaken to compare the pathogenicity of three species of Acanthamoeba in B6C3F1 mice after intranasal challenge with Acanthamoeba-induced cytopathogenicity for different macrophage populations. The ability of murine macrophage cell lines and activated murine peritoneal macrophages to lyse Acanthamoeba has been assessed by coincubating macrophages with 3H-uridine labeled amebae. Conversely, destruction of macrophages by Acanthamoeba was determined by measuring the release of chromium-51 from radiolabeled macrophages. Acanthamoeba culbertsoni, which is highly pathogenic for mice, destroys macrophage cultures in vitro. Activated primary peritoneal macrophages were more resistant to Acanthamoeba-mediated destruction than macrophage cell lines activated in vitro. Activated macrophages were capable of limited destruction of Acanthamoeba polyphaga and Acanthamoeba castellanii. Acanthamoeba-specific antibodies increased the amebicidal activity of activated macrophages. Macrophage-mediated destruction was by contact-dependent cytolysis and by ingestion of amebae. Conditioned medium obtained from macrophage cultures after treatment with lipopolysaccharide and interferon gamma was neither cytolytic nor cytostatic for Acanthamoeba spp. Purified recombinant cytokines including tumor necrosis factor alpha, interleukin 1 alpha, and interleukin 1 beta, alone or in combination, were not cytolytic for Acanthamoeba trophozoites.
Insights
Acanthamoeba culbertsoni destroys macrophages, while activated macrophages can lyse other Acanthamoeba species. Acanthamoeba-specific antibodies enhance this macrophage-mediated destruction, offering potential therapeutic insights.
Area of Science:
- Immunology
- Microbiology
- Parasitology
Background:
- Acanthamoeba species cause severe infections like amebic keratitis and encephalitis.
- Understanding host-pathogen interactions is crucial for developing treatments.
Purpose of the Study:
- To compare the pathogenicity of three Acanthamoeba species in mice.
- To investigate Acanthamoeba-induced cytopathogenicity in different macrophage populations.
- To assess macrophage-mediated destruction of Acanthamoeba.
Main Methods:
- Intranasal challenge of B6C3F1 mice with Acanthamoeba species.
- Coincubation of radiolabeled Acanthamoeba with macrophage cell lines and primary peritoneal macrophages.
- Measurement of macrophage lysis via chromium-51 release.
- Assessment of amebicidal activity with Acanthamoeba-specific antibodies.
Main Results:
- Acanthamoeba culbertsoni, a highly pathogenic species, destroyed macrophage cultures in vitro.
- Activated primary peritoneal macrophages exhibited greater resistance to Acanthamoeba-mediated destruction than in vitro-activated cell lines.
- Activated macrophages demonstrated limited destruction of Acanthamoeba polyphaga and Acanthamoeba castellanii.
- Acanthamoeba-specific antibodies enhanced the amebicidal activity of activated macrophages.
Conclusions:
- Macrophage-mediated destruction of Acanthamoeba occurs through contact-dependent cytolysis and phagocytosis.
- Cytokines like TNF-α, IL-1α, and IL-1β did not exhibit direct cytolytic or cytostatic effects on Acanthamoeba trophozoites.
- Activated macrophages play a role in controlling Acanthamoeba infections, with antibody enhancement offering a potential therapeutic strategy.