Research article - Peer-reviewed, 2020
The Chymase Mouse Mast Cell Protease-4 Regulates Intestinal Cytokine Expression in Mature Adult Mice Infected with Giardia intestinalis
Li, Zhiqiang; Peirasmaki, Dimitra; Svaerd, Staffan; Abrink, MagnusAbstract
Mast cells have been shown to affect the control of infections with the protozoan parasite Giardia intestinalis. Recently, we demonstrated that Giardia excretory-secretory proteins inhibited the activity of the connective tissue mast cell-specific protease chymase. To study the potential role of the chymase mouse mast cell protease (mMCP)-4 during infections with Giardia, mMCP-4(+/+) and mMCP-4(-/-) littermate mice were gavage-infected with G. intestinalis trophozoites of the human assemblage B isolate GS. No significant changes in weight gain was observed in infected young (approximate to 10 weeks old) mMCP-4(-/-) and mMCP-4(+/+) littermate mice. In contrast, infections of mature adult mice (>18 weeks old) caused significant weight loss as compared to uninfected control mice. We detected a more rapid weight loss in mMCP-4(-/-) mice as compared to littermate mMCP-4(+/+) mice. Submucosal mast cell and granulocyte counts in jejunum increased in the infected adult mMCP-4(-/-) and mMCP-4(+/+) mice. This increase was correlated with an augmented intestinal trypsin-like and chymotrypsin-like activity, but the myeloperoxidase activity was constant. Infected mice showed a significantly lower intestinal neutrophil elastase (NE) activity, and in vitro, soluble Giardia proteins inhibited human recombinant NE. Serum levels of IL-6 were significantly increased eight and 13 days post infection (dpi), while intestinal IL-6 levels showed a trend to significant increase 8 dpi. Strikingly, the lack of mMCP-4 resulted in significantly less intestinal transcriptional upregulation of IL-6, TNF-alpha, IL-25, CXCL2, IL-2, IL-4, IL-5, and IL-10 in the Giardia-infected mature adult mice, suggesting that chymase may play a regulatory role in intestinal cytokine responses.Keywords
mast cell; chymase; mMCP-4; infection; Giardia intestinalisPublished in
Cells2020, volume: 9, number: 4, article number: 925
Publisher: MDPI
Authors' information
Swedish University of Agricultural Sciences, Department of Biomedical Science and Veterinary Public Health
Peirasmaki, Dimitra
Uppsala Univ
Svaerd, Staffan
Uppsala Univ
Swedish University of Agricultural Sciences, Department of Biomedical Science and Veterinary Public Health
UKÄ Subject classification
Cell Biology
Publication Identifiers
DOI: https://doi.org/10.3390/cells9040925
URI (permanent link to this page)
https://res.slu.se/id/publ/106502