Abstract
BackgroundSerglycin proteoglycans are essential for maturation of secretory granules and for the correct granular storage of cationic proteases in hematopoietic cells, e.g. mast cells. However, little is known about the in vivo functions of serglycin proteoglycans during infection. Here we investigated the potential role of serglycin proteoglycans in host defense after infection with the nematode Trichinella spiralis.ResultsTwelve days post infection lack of serglycin proteoglycans caused significantly increased enteropathy. The serglycin-deficient mice showed significantly increased intestinal worm burden, reduced recruitment of mast cells to the intestinal crypts, decreased levels of the mast cell proteases MCPT5 and MCPT6 in intestinal tissue, decreased serum levels of TNF-α, IL-1β, IL-10 and IL-13, increased levels of IL-4 and total IgE in serum, and increased intestinal levels of the neutrophil markers myeloperoxidase and elastase, as compared to wild type mice. At five weeks post infection, increased larvae burden and inflammation were seen in the muscle tissue of the serglycin-deficient mice.ConclusionsOur results demonstrate that the serglycin-deficient mice were more susceptible to T. spiralis infection and displayed an unbalanced immune response compared to wild type mice. These findings point to an essential regulatory role of serglycin proteoglycans in immunity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12865-016-0155-y) contains supplementary material, which is available to authorized users.
Highlights
Serglycin proteoglycans are essential for maturation of secretory granules and for the correct granular storage of cationic proteases in hematopoietic cells, e.g. mast cells
Increased worm burden and enteropathy in T. spiralis infected serglycin-deficient mice To study the role of serglycin proteoglycans in an experimental T. spiralis infection model, wild type (WT) and SG−/− mice were inoculated with 500 infective muscle larvae by gavage
At 12 dpi the intestinal worm burden was significantly increased in SG−/− mice compared to WT mice indicating that serglycin proteoglycans are involved in the expulsion of T. spiralis (Fig. 1a)
Summary
Serglycin proteoglycans are essential for maturation of secretory granules and for the correct granular storage of cationic proteases in hematopoietic cells, e.g. mast cells. We investigated the potential role of serglycin proteoglycans in host defense after infection with the nematode Trichinella spiralis. Serglycin is a proteoglycan mainly found in secretory granules, expressed by several hematopoietic cell types [1]. In these cells, e.g. in cytotoxic T cells, natural killer (NK) cells, neutrophils, platelets and mast cells (MCs) the serglycin proteoglycans contribute to granular integrity [2], and in the serglycin-deficient (SG−/−) mouse strain the storage/retention of inflammatory mediators, i.e. cationic proteins, is impaired.
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