Abstract

The purpose of this study was to evaluate the potential of chitosan units released during natural degradation of the polymer to activate the immune system against T. spiralis infection. High molecular weight chitosan was injected intraperitoneally into C57BL/6 mice. Flow cytometry and cytokine concentration, measured by ELISA, were used to characterize peritoneal cell populations during T. spiralis infection. The strong chemo-attractive properties of chitosan caused considerable infiltration into the peritoneal cavity of CD11b+ cells, with reduced expression of MHC class II, CD80, CD86, Dectin-1 or CD23 receptors in comparison to T. spiralis-infected mice. After prolonged chitosan biodegradation, cell populations expressing IL-4R, MR and Dectin-1 receptors were found to coexist with elevated IL-6, IL-10, TGF-β and IgA production. IgA cross-reacted with T. spiralis antigen and chitosan. It was found that chitosan treatment attracted immune cells with low activity, which resulted in the number of nematodes increasing. The glucosamine and N-acetyl-D-glucosamine residues were recognized by wheat germ agglutinin (WGA) lectin and therefore any biodegradable chitosan units may actively downregulate the immune response to the parasite. The findings are relevant for both people and animals treated with chitosan preparations.

Highlights

  • There are many proposals for the use of polysaccharide biomaterials in medicine

  • The polymer acts as a temporary extracellular matrix; it is endocytosed by cells and eventually broken down by lysozyme, after which chitosan chains with low degrees of acetylation may remain active in the body for several months [9]

  • The aim of our studies was to evaluate the immune properties of naturally biodegraded chitosan units, which act as a model for the education of the immune system, and may determine their relevance in T. spiralis infection in mice

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Summary

Introduction

There are many proposals for the use of polysaccharide biomaterials in medicine. Due to their physical and chemical properties, many of these substances are suitable for therapeutic purposes [1,2]. Chitosan is soluble in dilute acids, and the number fraction of N-acetylglucosamine (GlcNAc) residues in the polymer chain, designated by the degree of acetylation, influences cell response by modulating the solubility, reactivity, biodegradability and activity of the polymer [10,11]. The larvae settle in myotubes, where they are encapsulated into nurse cells All these nematode stages act as sources of a plethora of signals detected by cell receptors on the columnar epithelium in the intestine and by cells of the innate immune system. Chitosan is well suited for evaluating the significance of glycans in the immune response; it is a potent source of high and low molecular-weight polymer chains or oligochains, which may allow functional immunoregulation supporting tissue regeneration [4]. The aim of our studies was to evaluate the immune properties of naturally biodegraded chitosan units, which act as a model for the education of the immune system, and may determine their relevance in T. spiralis infection in mice

Changes
Changes in the Percentage of Cells Expressing Immune Receptors
The Level of Cytokines in the Peritoneal Fluid
Myeloperoxidase
IgA Response
DAI andand were higher in the mice injected with chitosan
Biodegradation
Schedule of the Experiment
Flow Cytometry
Detection of IgA in the Peritoneal Fluid by ELISA
IgA Specific Response Detected by Electrophoresis and Immunoblotting
Histopathological Examination of Granuloma on the Surface of the Liver
Conclusions
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