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Macrophage Cholesterol Depletion and Its Effect on the Phagocytosis of Cryptococcus neoformans
Published on: December 19, 2014
Inhibition of Microbicidal Activity of Canine Macrophages DH82 Cell Line by Capsular Polysaccharides from
Isabel F LaRocque-de-Freitas1, Elias Barbosa da Silva-Junior2, Leticia Paixão Gemieski1
1Instituto de Veterinária, Universidade Federal Rural do Rio de Janeiro, Seropédica 23890-900, Brazil.
Abstract:
Cryptococcus neoformans is a lethal fungus that primarily affects the respiratory system and the central nervous system. One of the main virulence factors is the capsule, constituted by the polysaccharides glucuronoxylomannan (GXM) and glucuronoxylomanogalactan (GXMGal). Polysaccharides are immunomodulators. One of the target cell populations for modulation are macrophages, which are part of the first line of defense and important for innate and adaptive immunity. It has been reported that macrophages can be modulated to act as a "Trojan horse," taking phagocytosed yeasts to strategic sites or having their machinery activation compromised. The scarcity of information on canine cryptococcosis led us to assess whether the purified capsular polysaccharides from C. neoformans would be able to modulate the microbicidal action of macrophages. In the present study, we observed that the capsular polysaccharides, GXM, GXMGal, or capsule total did not induce apoptosis in the DH82 macrophage cell line. However, it was possible to demonstrate that the phagocytic activity was decreased after treatment with polysaccharides. In addition, recovered yeasts from macrophages treated with polysaccharides after phagocytosis could be cultured, showing that their viability was not altered. The polysaccharides led to a reduction in ROS production and the mRNA expression of IL-12 and IL-6. We observed that GXMGal inhibits MHC class II expression and GXM reduces ERK phosphorylation. In contrast, GXMGal and GXM were able to increase the PPAR-γ expression. Furthermore, our data suggest that capsular polysaccharides can reduce the microbicidal activity of canine macrophages DH82.
Insights
Cryptococcus neoformans capsular polysaccharides impair canine macrophage microbicidal activity by reducing phagocytosis and inflammatory responses. This suggests a novel mechanism of fungal immune evasion in canine cryptococcosis.
Area of Science:
- Mycology
- Immunology
- Veterinary Medicine
Background:
- Cryptococcus neoformans is a dangerous fungus impacting the respiratory and central nervous systems.
- The fungal capsule, composed of glucuronoxylomannan (GXM) and glucuronoxylomanogalactan (GXMGal), is a key virulence factor.
- Macrophages are crucial immune cells that can be modulated by fungal components, potentially aiding fungal survival.
Purpose of the Study:
- To investigate the effect of Cryptococcus neoformans capsular polysaccharides on the microbicidal activity of canine macrophages.
- To determine if GXM and GXMGal impact macrophage apoptosis, phagocytosis, and inflammatory signaling.
Main Methods:
- Treatment of DH82 canine macrophage cell line with purified GXM, GXMGal, or total capsule.
- Assessment of macrophage apoptosis, phagocytic activity, and yeast viability post-phagocytosis.
- Measurement of reactive oxygen species (ROS) production and mRNA expression of IL-12 and IL-6.
- Analysis of MHC class II, ERK phosphorylation, and PPAR-γ expression.
Main Results:
- Capsular polysaccharides did not induce apoptosis in DH82 macrophages.
- Phagocytic activity of macrophages was reduced, and yeast viability remained unaltered after phagocytosis.
- ROS production and mRNA expression of IL-12 and IL-6 were decreased.
- GXMGal inhibited MHC class II expression, while GXM reduced ERK phosphorylation.
- Both GXM and GXMGal increased PPAR-γ expression, suggesting a modulation of macrophage function.
Conclusions:
- Cryptococcus neoformans capsular polysaccharides can reduce the microbicidal activity of canine macrophages.
- These polysaccharides may play a role in fungal immune evasion by impairing macrophage function.
- Further research is needed to understand the full implications for canine cryptococcosis pathogenesis.
