Cryptococcus neoformans and its cell wall components induce similar cytokine profiles in human peripheral blood mononuclear cells despite differences in structure

Abstract

We studied the cytokine profile of peripheral blood mononuclear cells after stimulation with various cryptococcal strains or its purified cell wall components. After 3 h of stimulation, tumor necrosis factor (TNF) alpha levels were strongly increased, whereas interferon (IFN) gamma and interleukin (IL) 10 levels were increased only slightly, or not at all (respectively). In contrast, after 18 h, TNF-alpha and IFN-gamma levels were (strongly) decreased, whereas the IL-10 levels were increased. The IL-1beta, IL-6 and IL-8 levels were equally high throughout the experiment. In order to establish which of the cryptococcal envelope components contributed most to the observed cytokine profile induced by whole cryptococci, glucuronoxylomannan, galactoxylomannan and mannoproteins were purified and partially characterized biochemically. All cryptococcal components elicited a similar cytokine pattern despite the differences in structure.

Aggregation ofCryptococcus neoformansby Surfactant Protein D Is Inhibited by Its Capsular Component Glucuronoxylomannan

“…The carbohydrate moieties of both MPs have very similar monosaccharide compositions, containing high percentages of residues for which SP-D has high affinity when these residues are presented as monosaccharides (42). However, only MP1 is a ligand for SP-D, which further emphasizes the great importance of the actual bonding and orientation of the monosaccharide residues.…”

“…made up of a large carbohydrate part linked to a relatively small peptide part (7 to 17% of the total mass) (42).…”

Evidence of a Role for Monocytes in Dissemination and Brain Invasion byCryptococcus neoformans

“…Cryptococcal infection is associated with limited inflammation, but low concentrations of proinflammatory cytokines and chemokines, such as tumor necrosis factor alpha, gamma interferon, macrophage inflammatory protein 1␣, and monocyte chemoattractant protein 1, during cryptococcosis could enhance leukocyte recruitment and subsequent organ reseeding by infected phagocytes (1,20,29,30,55). In experiments performed in the early 1980s, Monga showed that depletion of tissue macrophages by treatment with silica prior to infection enhanced susceptibility to infection (39).…”

Potent Inhibition of Neutrophil Migration by Cryptococcal Mannoprotein-4-Induced Desensitization

“…⌬CneF used in the assays was diluted 3-fold. MPs were purified from ⌬CneF, as described recently (30). Briefly, ⌬CneF was dialyzed against excess mQ water, freeze dried, and applied to a 100-ml Con A Sepharose-4B column.…”

“…Therefore, we set out to characterize the component of ⌬CneF responsible for the inhibition. To assess this, we first optimized the current protocol for isolating capsular Ags and purified the most important constituents of ⌬CneF (GalXM, MP-1, MP-2, and MP-4) to near homogeneity (30). We found that MP-4 was primarily responsible for the inhibition of PMN migration.…”