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Research article2021Peer reviewedOpen access

Serglycin-Deficiency Causes Reduced Weight Gain and Changed Intestinal Cytokine Responses in Mice Infected With Giardia intestinalis

Li, Zhiqiang; Peirasmaki, Dimitra; Svard, Staffan; Abrink, Magnus

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 (asymptotic to 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-alpha and CXCL2, and increased IFN-gamma, 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.

Keywords

serglycin proteoglycan; knockout mouse; infection; Giardia intestinalis; innate intestinal immunity

Published in

Frontiers in Immunology
2021, Volume: 12, article number: 677722
Publisher: FRONTIERS MEDIA SA

      SLU Authors

      • UKÄ Subject classification

      Immunology in the medical area

      Publication identifier

      DOI: https://doi.org/10.3389/fimmu.2021.677722

      Permanent link to this page (URI)

      https://res.slu.se/id/publ/113303