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01.12.2016 | Research article | Ausgabe 1/2016 Open Access

BMC Immunology 1/2016

Serglycin proteoglycans limit enteropathy in Trichinella spiralis-infected mice

Zeitschrift:
BMC Immunology > Ausgabe 1/2016
Autoren:
Ananya Roy, Osama Sawesi, Ulrika Pettersson, Anders Dagälv, Lena Kjellén, Anna Lundén, Magnus Åbrink
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12865-016-0155-y) contains supplementary material, which is available to authorized users.

Abstract

Background

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. 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.

Results

Twelve 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.

Conclusions

Our 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.
Zusatzmaterial
Additional file 3: Figure S2. T. spiralis induced entheropathy in serglycin-deficient mice reconstituted with bone marrow derived wild type MCs and in heparin-deficient NDST2−/− mice (12 dpi). The SG−/− mice were reconstituted with 5 x106 WT MCs administered intraperitoneally and 8 weeks later infected with T. spiralis. (a) a representative intestinal section of the infected RSG−/− mice stained with Toluidine blue (pH < 2.0), and (b) a representative cytospin slide of peritoneal cells from an infected RSG−/− mice stained with May-Grünwald/Giemsa. Arrowheads mark the stained MCs. Paraffin embedded intestinal tissues from uninfected and infected WT, SG−/−, MC-reconstituted SG−/− (RSG−/−), and NDST2−/− mice, were sectioned and stained with H&E, and histopathological changes analyzed using Nikon NIS software. (c) MC-counts in chloroacetate esterase stained intestinal tissue, (d) intestinal worm burden, and (e) T. spiralis specific IgG levels in serum. In (f) the villus length, and (g) the swelling of the villi tips was measured of 15 villi per intestinal section as described in M&M. In (h) the epithelial lesion of the villus tip (as defined in Material and Methods) was counted in 10 intact villi per infected mouse. Data from one experiment is shown, with infected mice (N = 4 for RSG−/− and SG−/−, N = 5 for WT and NDST2−/−) and with control mice (N = 3). Data is expressed as mean values (c, d, f-h) and mean + SEM (e), and significant differences between genotypes are indicated in the figure. Not significant, ns P >0.05, *P ≤0.05, **P <0.001, versus infected WT, and not significant (ns) P >0.05, ++P <0.001 versus infected SG−/− mice, respectively. (TIF 9451 kb)
Additional file 5: Figure S4. Reconstitution with WT bone marrow derived MCs in serglycin-deficient mice does not dampen the enhanced neutrophil activity (at 12 dpi). Serglycin proteoglycans seem to influence neutrophil and eosinophil activities in T. spiralis infected mice (see Fig. 4 in the main text), and to assess neutrophil and eosinophil recruitment in intestinal tissue in infected serglycin-deficient mice repaired with WT MCs, we measured the enzymatic activities of (a) myeloperoxidase (MPO) and (b) neutrophil elastase (NE). In a and b data from one reconstitution experiment is shown with control mice (N = 3) and with infected mice (N = 4 for RSG−/− and SG−/−, N = 5 for WT and NDST2−/−). Data is expressed as mean + SEM and significant differences are indicated in the figure. ##P <0.001, ###P <0.0001 versus infected mice. Not significant, ns P >0.05, **P <0.001, ***P <0.0001 versus infected WT mice, and not significant (ns) P >0.05, +++P <0.0001 versus infected SG−/− mice, respectively. (TIF 397 kb)
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