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
Summary
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]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
