Ingestion of Candida albicans down-regulates mannose receptor expression on rat macrophages.

Abstract

The frequency of infection and death due to various Candida species has increased steadily during the past decade, with mucocutaneous candidal infections as a common problem in the immunocompromised host. Mononuclear phagocytes are important in phagocytosis of this organism. In areas where there are low levels of opsonins, the macrophage-specific mannose receptor plays a dominant role in mediating Candida albicans ingestion. Following receptor-mediated infection, the host macrophage produces inflammatory cytokines and mediators that lead to ultimate killing of the invading Candida. Infection of macrophages by pathogens often leads to altered function that might effect their subsequent host defense properties. For example, function of both the complement receptor type 3 and the mannose receptor are down-regulated following exposure to pathogens or pathogen-derived products. In the current study, we have examined the down-regulation of mannose receptor expression following Candida infection and have investigated possible mechanisms that might be involved. Mannose receptor activity was decreased following 24 h postinfection with Candida. Both tumor necrosis factor and nitric oxide were produced during the infection, and inhibition of the these mediators partially blocked the effect on the receptor. Infection with Candida also inhibited the ability of dexamethasone to up-regulate mannose receptor expression. Finally, mannose receptor protein turnover was accelerated in Candida-infected macrophages. We conclude that Candida down-regulates one of the receptors involved in its internalization through a combination of production of modulatory molecules and enhanced receptor degradation. These results support the hypothesis that pathogens that infect macrophages have the ability to alter the phagocytic pathways available for subsequent host defense.

• Authors: V L Shepherd, K B Lane, R Abdolrasulnia
• Journal: Archives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 344 Issue 2 Pg. 350-6 (Aug 15 1997) ISSN: 0003-9861 [Print] United States
• PMID: 9264549 (Publication Type: Journal Article)

Chemical References

• Enzyme Inhibitors
• Lectins, C-Type
• Mannose Receptor
• Mannose-Binding Lectins
• Receptors, Cell Surface
• Tumor Necrosis Factor-alpha
• omega-N-Methylarginine
• Nitric Oxide
• Dexamethasone
• Horseradish Peroxidase

Topics

• Animals
• Candida albicans (metabolism, pathogenicity)
• Dexamethasone (pharmacology)
• Down-Regulation
• Electrophoresis, Polyacrylamide Gel
• Enzyme Inhibitors (pharmacology)
• Horseradish Peroxidase (metabolism)
• Lectins, C-Type
• Macrophages (metabolism, microbiology)
• Mannose Receptor
• Mannose-Binding Lectins
• Nitric Oxide (metabolism)
• Phagocytosis
• Rats
• Rats, Sprague-Dawley
• Receptors, Cell Surface (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)
• Up-Regulation
• omega-N-Methylarginine (pharmacology)