{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:08:23Z","timestamp":1790615303528,"version":"4.1.0"},"reference-count":81,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,9]],"date-time":"2020-04-09T00:00:00Z","timestamp":1586390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2012-03364"],"award-info":[{"award-number":["2012-03364"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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\u2212\/\u2212 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 (\u224810 weeks old) mMCP-4\u2212\/\u2212 and mMCP-4+\/+ littermate mice. In contrast, infections of mature adult mice (&gt;18 weeks old) caused significant weight loss as compared to uninfected control mice. We detected a more rapid weight loss in mMCP-4\u2212\/\u2212 mice as compared to littermate mMCP-4+\/+ mice. Submucosal mast cell and granulocyte counts in jejunum increased in the infected adult mMCP-4\u2212\/\u2212 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-\u03b1, 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.<\/jats:p>","DOI":"10.3390\/cells9040925","type":"journal-article","created":{"date-parts":[[2020,4,9]],"date-time":"2020-04-09T14:42:03Z","timestamp":1586443323000},"page":"925","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The Chymase Mouse Mast Cell Protease-4 Regulates Intestinal Cytokine Expression in Mature Adult Mice Infected with Giardia intestinalis"],"prefix":"10.3390","volume":"9","author":[{"given":"Zhiqiang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, SE-75007 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Peirasmaki","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Uppsala University, SE-75124 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Staffan","family":"Sv\u00e4rd","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Uppsala University, SE-75124 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1335-3927","authenticated-orcid":false,"given":"Magnus","family":"\u00c5brink","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, SE-75007 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Caccio, S.M., Lalle, M., and Svard, S.G. 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