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Differences in outcome of the interaction between Cryptococcus neoformans glucuronoxylomannan and human monocytes and
Claudia Monari1, Cinzia Retini, Arturo Casadevall
1Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Abstract:
Disseminated infections by the opportunistic yeast Cryptococcus neoformans are characterized by accumulation in tissues of glucuronoxylomannan (GXM), the major component of the capsular polysaccharide. We investigated binding, uptake, and disposal of GXM by peripheral blood neutrophils and monocytes, and the effect of GXM uptake on phagocytic cell function. GXM was efficiently bound and internalized by both types of phagocytic cells, with maximal loading at 50 microg/ml, a GXM concentration found in serum and cerebrospinal fluid of some cryptococcosis patients. However, substantial differences were noted in the kinetics for uptake by macrophages and neutrophils. Whereas neutrophils rapidly ingested limited amounts of GXM and then expelled or degraded it after 1 h of incubation, macrophages demonstrated continuous intracellular accumulation for up to 1 week of incubation. Accumulation of GXM by neutrophils was accompanied by reduced anticryptococcal activity, suggesting one more mechanism for virulence enhancement by the major capsular component of C. neoformans.
Insights
Cryptococcus neoformans glucuronoxylomannan (GXM) is taken up by immune cells. Neutrophils internalize and degrade GXM, impairing their antifungal activity, while macrophages accumulate it.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Disseminated Cryptococcus neoformans infections involve glucuronoxylomannan (GXM), a major capsular polysaccharide.
- GXM accumulation in tissues is a hallmark of cryptococcosis.
- Understanding GXM-phagocyte interactions is crucial for cryptococcosis pathogenesis.
Purpose of the Study:
- To investigate the binding, uptake, and disposal of GXM by human peripheral blood neutrophils and monocytes.
- To determine the effect of GXM uptake on phagocytic cell function, specifically anticryptococcal activity.
Main Methods:
- Incubation of human neutrophils and monocytes with purified GXM.
- Quantification of GXM uptake and intracellular accumulation over time.
- Assessment of anticryptococcal activity of phagocytes post-GXM exposure.
Main Results:
- Both neutrophils and monocytes efficiently bound and internalized GXM, with maximal uptake at 50 microg/ml.
- Neutrophils rapidly ingested and then expelled or degraded GXM within 1 hour.
- Macrophages exhibited continuous intracellular GXM accumulation for up to one week.
- GXM accumulation by neutrophils correlated with reduced anticryptococcal activity.
Conclusions:
- Phagocytic cells, particularly neutrophils, interact differently with Cryptococcus neoformans GXM.
- Neutrophil GXM uptake and subsequent degradation/expulsion may impair their ability to combat cryptococcosis.
- This interaction represents a potential mechanism by which GXM enhances Cryptococcus neoformans virulence.