Abstract

The proteoglycan serglycin (SG) is expressed by different innate and adaptive immune cells, e.g. mast cells, macrophages, neutrophils, and cytotoxic T lymphocytes, where SG contributes to correct granule storage and extracellular activity of inflammatory mediators. Here the serglycin-deficient (SG−/−) mouse strain was used to investigate the impact of SG on intestinal immune responses during infection with the non-invasive protozoan parasite Giardia intestinalis. Young (≈11 weeks old) oral gavage-infected congenic SG−/− mice showed reduced weight gain as compared with the infected SG+/+ littermate mice and the PBS-challenged SG−/− and SG+/+ littermate mice. The infection caused no major morphological changes in the small intestine. However, a SG-independent increased goblet cell and granulocyte cell count was observed, which did not correlate with an increased myeloperoxidase or neutrophil elastase activity. Furthermore, infected mice showed increased serum IL-6 levels, with significantly reduced serum IL-6 levels in infected SG-deficient mice and decreased intestinal expression levels of IL-6 in the infected SG-deficient mice. In infected mice the qPCR analysis of alarmins, chemokines, cytokines, and nitric oxide synthases (NOS), showed that the SG-deficiency caused reduced intestinal expression levels of TNF-α and CXCL2, and increased IFN-γ, CXCL1, and NOS1 levels as compared with SG-competent mice. This study shows that SG plays a regulatory role in intestinal immune responses, reflected by changes in chemokine and cytokine expression levels and a delayed weight gain in young SG−/− mice infected with G. intestinalis.

Highlights

  • Giardia intestinalis is a non-invasive protozoan intestinal parasite found worldwide

  • When G. intestinalis attach to the microvillus brush border of the intestinal epithelial cells, the cells respond by producing chemokines and cytokines, which attracts immune cells to the intestinal submucosa [10,11,12]

  • SG-deficiency has a negative effect on weight gain during G. intestinalis infections but it cannot be correlated to the amount of parasite DNA in fecal material

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Summary

Introduction

Giardia intestinalis ( named G. lamblia or G. duodenalis) is a non-invasive protozoan intestinal parasite found worldwide. Giardia spp. secrete no known toxins, still infections contribute to more than 200 million human diarrhea cases per year [3] Since 1954, at least 132 water-borne outbreaks of giardiasis have been reported worldwide [4]. When G. intestinalis attach to the microvillus brush border of the intestinal epithelial cells, the cells respond by producing chemokines and cytokines, which attracts immune cells to the intestinal submucosa [10,11,12]. Both innate and adaptive immunity, with a mixed Th1/Th2/Th17 response profile, play significant roles in the host defence towards G. intestinalis [13,14,15]. During infection G. intestinalis secretes a large number of immunomodulatory proteins, which possibly regulates the host intestinal immune responses [16,17,18,19]

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