Serglycin proteoglycans limit enteropathy in Trichinella spiralis-infected mice.
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.



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.



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.
Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.|Department of Biomedical Sciences and Veterinary Public Health, Section of Immunology, Swedish University of Agricultural Sciences, VHC, Box 7028, 75007, Uppsala, Sweden.
Ananya
A
Roy
Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.|Department of Biomedical Sciences and Veterinary Public Health, Section of Immunology, Swedish University of Agricultural Sciences, VHC, Box 7028, 75007, Uppsala, Sweden.
Osama
O
Sawesi
Department of Pathology and Wildlife Diseases, The National Veterinary Institute, Uppsala, Sweden.
Ulrika
U
Pettersson
Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Anders
A
Dagälv
Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Lena
L
Kjellén
Department of Microbiology, The National Veterinary Institute, Uppsala, Sweden.|Department of Biomedical Sciences and Veterinary Public Health, Section of Immunology, Swedish University of Agricultural Sciences, VHC, Box 7028, 75007, Uppsala, Sweden.
Anna
A
Lundén
Department of Biomedical Sciences and Veterinary Public Health, Section of Immunology, Swedish University of Agricultural Sciences, VHC, Box 7028, 75007, Uppsala, Sweden. magnus.abrink@slu.se.
Magnus
M
Åbrink
D000818:Animals; D002465:Cell Movement; D053818:Chymases / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D018928:Immunity, Mucosal; D007411:Intestinal Diseases, Parasitic / Q000276:immunology*; D007422:Intestines / Q000276:immunology* / Q000469:parasitology; D008407:Mast Cells / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology*; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D058408:Th1-Th2 Balance; D017160:Trichinella spiralis / Q000276:immunology*; D014235:Trichinellosis / Q000276:immunology*; D053802:Tryptases / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
D016207:Cytokines; D011509:Proteoglycans; C509190:Tpsb2 protein, mouse; D033921:Vesicular Transport Proteins; C075430:serglycin; C509227:Cma1 protein, mouse; D053818:Chymases; D053802:Tryptases
Infection; Intestine; Mast cell; Parasite; Serglycin; Trichinella spiralis