ABSTRACT
Lipid bodies [lipid droplets (LBs)] are lipid-rich organelles involved in lipid metabolism, signalling and inflammation. Recent findings suggest a role for LBs in host response to infection; however, the potential functions of this organelle in Toxoplasma gondii infection and how it alters macrophage microbicidal capacity during infection are not well understood. Here, we investigated the role of host LBs in T. gondii infection in mouse peritoneal macrophages in vitro. Macrophages cultured with mouse serum (MS) had higher numbers of LBs than those cultured in foetal bovine serum and can function as a model to study the role of LBs during intracellular pathogen infection. LBs were found in association with the parasitophorous vacuole, suggesting that T. gondii may benefit from this lipid source. Moreover, increased numbers of macrophage LBs correlated with high prostaglandin E2 (PGE2) production and decreased nitric oxide (NO) synthesis. Accordingly, LB-enriched macrophages cultured with MS were less efficient at controlling T. gondii growth. Treatment of macrophages cultured with MS with indomethacin, an inhibitor of PGE2 production, increased the microbicidal capacity against T. gondii. Collectively, these results suggest that culture with MS caused a decrease in microbicidal activity of macrophages against T. gondii by increasing PGE2 while lowering NO production.
Subject(s)
Animals , Cattle , Male , Mice , Lipid Droplets/parasitology , Macrophage Activation/physiology , Macrophages, Peritoneal/parasitology , Toxoplasma/physiology , Vacuoles/parasitology , Host-Parasite Interactions , Indomethacin/pharmacology , Lipid Droplets/physiology , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Macrophages, Peritoneal/chemistry , Macrophages, Peritoneal/physiology , Macrophages, Peritoneal/ultrastructure , Nitric Oxide/biosynthesis , Primary Cell Culture , Prostaglandins E/antagonists & inhibitors , Prostaglandins E/biosynthesis , Vacuoles/physiologyABSTRACT
Macrophages release more than one hundred compounds into the extracellular environment. Among these, there are cytokines and intermediate oxigen compounds, such as TNF-"ALPHA" and 'H POT. 2''O POT. 2'. We evaluated the effect of the crude essential oil of Achillea millefolium L. (Asteraceae) by determining hydrogen peroxide ('H POT. 2''O POT. 2') and tumor necrosis factor-a (TNF-"ALPHA") release in cultures of peritoneal macrophages cells from Swiss mice. Commercial azulene was also tested for comparison with the essential oil. The macrophages viability in the presence of the oil was analyzed and dilutions of 1:100 and 1:200 showed the best results. A mild production of 'H POT. 2''O POT. 2' and a moderate liberation of TNF-"ALPHA" were observed...
Subject(s)
Mice , Animals , Macrophages, Peritoneal/ultrastructure , Millefolium , Oils, Volatile/analysis , Hydrogen Peroxide/analysis , Tumor Necrosis Factor-alpha , Centrifugation , Chromatography, Thin LayerABSTRACT
Salmonella typhi is a facultative intracellular human specific pathogen. Both immunocompetent and immunodeficient mice are resistant to S. typhi. However, when they are infected with S. typhi suspended in mucin, the bacteria become pathogenic and infect peritoneal phagocytic cells. The LD50 for mice was 10(5) bacteria suspended in 5 percent mucin; mouse survival was approximately 48 hours after injection. A high number of bacteria was recovered from peritoneal cells; transmission electron microscopy disclosed a large number of vesicles filled with S. typhi cells in peritoneal cells from infected animals. The addition of mucin to cultures of the reticuloendothelial cell line J774.3 also allowed invasion of the mammalian cells with S. typhi. These data indicate that mucin allows intracellular survival of S. typhi