Secreted Giardia intestinalis cysteine proteases disrupt intestinal epithelial cell junctional complexes and degrade chemokines

Liu, Jingyi; Ma'ayeh, Showgy; Peirasmaki, Dimitra; Lundström-Stadelmann, Britta; Hellman, Lars; Svärd, Staffan G. (2018). Secreted Giardia intestinalis cysteine proteases disrupt intestinal epithelial cell junctional complexes and degrade chemokines. Virulence, 9(1), pp. 879-894. Taylor & Francis 10.1080/21505594.2018.1451284

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Giardiasis is a common diarrheal disease caused by the protozoan parasite Giardia intestinalis. Cysteine proteases (CPs) are acknowledged as virulence factors in Giardia but their specific role in the molecular pathogenesis of disease is not known. Herein, we aimed to characterize the three main secreted CPs (CP14019, CP16160 and CP16779), which were identified by mass spectrometry in the medium during interaction with intestinal epithelial cells (IECs) in vitro. First, the CPs were epitope-tagged and localized to the endoplasmic reticulum and cytoplasmic vesicle-like structures. Second, we showed that recombinant CPs, expressed in Pichia pastoris, are more active in acidic environment (pH 5.5-6) and we determined the kinetic parameters using fluorogenic substrates. Third, excretory-secretory proteins (ESPs) from Giardia trophozoites affect the localization of apical junctional complex (AJC) proteins and recombinant CPs cleave or re-localize the AJC proteins (claudin-1 and -4, occludin, JAM-1, β-catenin and E-cadherin) of IECs. Finally, we showed that the ESPs and recombinant CPs can degrade several chemokines, including CXCL1, CXCL2, CXCL3, IL-8, CCL2, and CCL20, which are up-regulated in IECs during Giardia-host cell interactions. This is the first study that characterizes the role of specific CPs secreted from Giardia and our results collectively indicate their roles in the disruption of the intestinal epithelial barrier and modulating immune responses during Giardia infections.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology
05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction

UniBE Contributor:

Lundström Stadelmann, Britta

Subjects:

600 Technology > 630 Agriculture

ISSN:

2150-5608

Publisher:

Taylor & Francis

Language:

English

Submitter:

Britta Lundström Stadelmann

Date Deposited:

08 Nov 2018 09:00

Last Modified:

22 Oct 2019 17:47

Publisher DOI:

10.1080/21505594.2018.1451284

PubMed ID:

29726306

BORIS DOI:

10.7892/boris.120971

URI:

https://boris.unibe.ch/id/eprint/120971

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