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Giardia excretory-secretory proteins modulate the enzymatic activities of mast cell chymase and tryptase
Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, SE-75007 Uppsala, Sweden.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.ORCID iD: 0000-0002-7392-1746
Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, SE-75007 Uppsala, Sweden.
2019 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 114, p. 535-544Article in journal (Refereed) Published
Abstract [en]

Background

Mast cells are involved in the host immune response controlling infection with the non-invasive intestinal protozoan parasite Giardia intestinalis. Experimental infections in rodents with G. intestinalis showed increased intestinal expression of mucosal and connective mast cell specific proteases suggesting that both mucosal and connective tissue mast cells are recruited and activated during infection. During infection Giardia excretory-secretory proteins (ESPs) with immunomodulatory capacity are released. However, studies investigating potential interactions between Giardia ESPs and the connective tissue mast cell specific serine proteases, i.e. human chymase and mouse mast cell protease (mMCP)-4 and, human and mouse tryptase (mMCP-6) remain scarce.

Results

We first investigated if soluble Giardia proteins (sGPs), which over-lap extensively in protein content with ESP fractions, from the isolates GS, WB and H3, could induce mast cell activation. sGPs induced a minor activation of bone marrow derived mucosal-like mast cells, as indicated by increased IL-6 secretion and no degranulation. Furthermore, sGPs were highly resistant to degradation by human tryptase while human chymase degraded a 65 kDa sGP and, wild-type mouse ear tissue extracts degraded several protein bands in the 10 to 75 kDa range. In striking contrast, sGPs and ESPs were found to increase the enzymatic activity of human and mouse tryptase and to reduce the activity of human and mouse chymase.

Conclusion

Our finding suggests that Giardia ssp. via enhancement or reduction of mast cell protease activity may modulate mast cell-driven intestinal immune responses. ESP-mediated modulation of the mast cell specific proteases may also increase degradation of tight junctions, which may be beneficial for Giardia ssp. during infection.

Place, publisher, year, edition, pages
2019. Vol. 114, p. 535-544
Keywords [en]
Mast cell, Tryptase, Chymase, Infection, Giardia ssp., Parasite, Intestine, Giardia excretory-secretory proteins (ESPs)
National Category
Immunology Infectious Medicine
Identifiers
URN: urn:nbn:se:uu:diva-396740DOI: 10.1016/j.molimm.2019.07.024ISI: 000490625600050PubMedID: 31518857OAI: oai:DiVA.org:uu-396740DiVA, id: diva2:1373125
Funder
Swedish Research CouncilAvailable from: 2019-11-26 Created: 2019-11-26 Last updated: 2019-11-26Bibliographically approved

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Peirasmaki, DimitraSvärd, Staffan

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