Abstract
An important virulence factor of the pathogenic fungus Cryptococcus neoformans is its polysaccharide capsule. The capsular polysaccharides glucuronoxylomannan (GXM), galactoxylomannan (GalXM) and the mannoproteins (MPs) display various immunomodulatory effects on the host response, such as the inhibition of phagocytosis, suppression of T-cell mediated immunity, and induction of immunogenic tolerance. Moreover, these capsular polysaccharides are able to interfere with the migration of phagocytes despite adequate stimulation of chemokine production and their concerted action accounts for the mild inflammatory response often observed in cryptococcosis. Different mechanisms contribute to this phenomenon. First, cryptococcal polysaccharides impair leukocyte migration towards chemoattractants. A combination of the intrinsic chemoattracting properties of circulating polysaccharides and the ability to induce cross-desensitization of chemokine receptors prevents leukocytes from leaving the bloodstream and migrating towards inflammatory site. Polysaccharide-induced repressive effects on the C5a receptor expression on neutrophils may also add to this impaired chemokinesis. Second, polysaccharides interfere with leukocyte adhesion to and migration through the endothelium. Both GXM and MP-4 induce L-selectin shedding from the surface of leukocytes; hence, interference with leukocyte rolling on the endothelium can be expected. GXM also interferes with the subsequent process of firm leukocyte adhesion to the endothelium in vitro. Thirdly, capsular polysaccharides enhance the production of anti-inflammatory interleukin-10 (IL-10) and induce tumor necrosis factor-alpha (TNFα) receptor loss from the surface of neutrophils. The capacity to reduce neutrophil influx makes cryptococcal polysaccharides interesting compounds to study in clinical models of inflammation (i.e.; sepsis, auto-immune disorders) in which leukocyte influx can be potentially damaging to host tissues.
Keywords: cryptococcus neoformans, polysaccharides, leukocyte migration, chemokines, cytokines
Current Medicinal Chemistry
Title: Effects of the Capsular Polysaccharides of Cryptococcus neoformans on Phagocyte Migration and Inflammatory Mediators [General Articles]
Volume: 11 Issue: 2
Author(s): Pauline M. Ellerbroek, M. E. Annemiek, Walenkamp, Andy I.M. Hoepelman and Frank E.J. Coenjaerts
Affiliation:
Keywords: cryptococcus neoformans, polysaccharides, leukocyte migration, chemokines, cytokines
Abstract: An important virulence factor of the pathogenic fungus Cryptococcus neoformans is its polysaccharide capsule. The capsular polysaccharides glucuronoxylomannan (GXM), galactoxylomannan (GalXM) and the mannoproteins (MPs) display various immunomodulatory effects on the host response, such as the inhibition of phagocytosis, suppression of T-cell mediated immunity, and induction of immunogenic tolerance. Moreover, these capsular polysaccharides are able to interfere with the migration of phagocytes despite adequate stimulation of chemokine production and their concerted action accounts for the mild inflammatory response often observed in cryptococcosis. Different mechanisms contribute to this phenomenon. First, cryptococcal polysaccharides impair leukocyte migration towards chemoattractants. A combination of the intrinsic chemoattracting properties of circulating polysaccharides and the ability to induce cross-desensitization of chemokine receptors prevents leukocytes from leaving the bloodstream and migrating towards inflammatory site. Polysaccharide-induced repressive effects on the C5a receptor expression on neutrophils may also add to this impaired chemokinesis. Second, polysaccharides interfere with leukocyte adhesion to and migration through the endothelium. Both GXM and MP-4 induce L-selectin shedding from the surface of leukocytes; hence, interference with leukocyte rolling on the endothelium can be expected. GXM also interferes with the subsequent process of firm leukocyte adhesion to the endothelium in vitro. Thirdly, capsular polysaccharides enhance the production of anti-inflammatory interleukin-10 (IL-10) and induce tumor necrosis factor-alpha (TNFα) receptor loss from the surface of neutrophils. The capacity to reduce neutrophil influx makes cryptococcal polysaccharides interesting compounds to study in clinical models of inflammation (i.e.; sepsis, auto-immune disorders) in which leukocyte influx can be potentially damaging to host tissues.
Export Options
About this article
Cite this article as:
Ellerbroek M. Pauline, E. Annemiek M. , Walenkamp , Andy I.M. Hoepelman and Coenjaerts E.J. Frank, Effects of the Capsular Polysaccharides of Cryptococcus neoformans on Phagocyte Migration and Inflammatory Mediators [General Articles], Current Medicinal Chemistry 2004; 11 (2) . https://dx.doi.org/10.2174/0929867043456188
DOI https://dx.doi.org/10.2174/0929867043456188 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Renal Cytochrome P450-Derived Eicosanoids and Hypertension
Current Hypertension Reviews Perfusion MRI of Brain Neoplams
Current Medical Imaging Recent Developments of C-Aryl Glucoside SGLT2 Inhibitors
Current Medicinal Chemistry PDE4D Gene in the STRK1 Region on 5q12: Susceptibility Gene for Ischemic Stroke
Current Medicinal Chemistry Catastrophic Antiphospholipid Syndrome - 20 Years Later
Current Rheumatology Reviews Synthetic and Natural Coumarins as Cytotoxic Agents
Current Medicinal Chemistry - Anti-Cancer Agents New Pharmacological Approaches in Infants with Hypoxic-Ischemic Encephalopathy
Current Pharmaceutical Design New Horizons in the Treatment of Neurological Disorders with Tailorable Gold Nanoparticles
Current Drug Metabolism Targeted Therapies in the Treatment of Advanced Renal Cell Carcinoma
Recent Patents on Anti-Cancer Drug Discovery Pulmonary Arterial Hypertension in HIV-infected Patients
Current Hypertension Reviews Snake Venom Metalloproteinases: Structure, Mechanism and Induced Diseases
Current Chemical Biology Neuroprotective Effects of Ginkgolide B Against Ischemic Stroke: A Review of Current Literature
Current Topics in Medicinal Chemistry Repositioning of Drugs in Cardiometabolic Disorders: Importance and Current Scenario
Current Topics in Medicinal Chemistry The Role of Renal Nerve Ablation for the Management of Resistant Hypertension and other Disease Conditions: Benefits and Concerns
Current Vascular Pharmacology Mast Cell – Glia Dialogue in Chronic Pain and Neuropathic Pain: Blood-Brain Barrier Implications
CNS & Neurological Disorders - Drug Targets Therapy Against Ischemic Injury
Current Pharmaceutical Design Vasopressin Receptor Antagonists in Heart Failure
Recent Patents on Cardiovascular Drug Discovery Adoptive Regulatory T-cell Therapy Attenuates Subarachnoid Hemor-rhage-induced Cerebral Inflammation by Suppressing TLR4/NF-B Signaling Pathway
Current Neurovascular Research Cucurbitacin E, An Experimental Lead Triterpenoid with Anticancer, Immunomodulatory and Novel Effects Against Degenerative Diseases. A Mini-Review
Current Topics in Medicinal Chemistry Gene Therapy in In Vivo Isolated Perfusion Models
Current Gene Therapy