Characterization of the Giardia intestinalis secretome during interaction with human intestinal epithelial cells: The impact on host cells.
BACKGROUND:Giardia intestinalis is a non-invasive protozoan parasite that causes giardiasis in humans, the most common form of parasite-induced diarrhea. Disease mechanisms are not completely defined and very few virulence factors are known. METHODOLOGY:To identify putative virulence factors and elu...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-12-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | http://europepmc.org/articles/PMC5739509?pdf=render |
| _version_ | 1818007777993293824 |
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| author | Showgy Y Ma'ayeh Jingyi Liu Dimitra Peirasmaki Katarina Hörnaeus Sara Bergström Lind Manfred Grabherr Jonas Bergquist Staffan G Svärd |
| author_facet | Showgy Y Ma'ayeh Jingyi Liu Dimitra Peirasmaki Katarina Hörnaeus Sara Bergström Lind Manfred Grabherr Jonas Bergquist Staffan G Svärd |
| author_sort | Showgy Y Ma'ayeh |
| collection | DOAJ |
| description | BACKGROUND:Giardia intestinalis is a non-invasive protozoan parasite that causes giardiasis in humans, the most common form of parasite-induced diarrhea. Disease mechanisms are not completely defined and very few virulence factors are known. METHODOLOGY:To identify putative virulence factors and elucidate mechanistic pathways leading to disease, we have used proteomics to identify the major excretory-secretory products (ESPs) when Giardia trophozoites of WB and GS isolates (assemblages A and B, respectively) interact with intestinal epithelial cells (IECs) in vitro. FINDINGS:The main parts of the IEC and parasite secretomes are constitutively released proteins, the majority of which are associated with metabolism but several proteins are released in response to their interaction (87 and 41 WB and GS proteins, respectively, 76 and 45 human proteins in response to the respective isolates). In parasitized IECs, the secretome profile indicated effects on the cell actin cytoskeleton and the induction of immune responses whereas that of Giardia showed anti-oxidation, proteolysis (protease-associated) and induction of encystation responses. The Giardia secretome also contained immunodominant and glycosylated proteins as well as new candidate virulence factors and assemblage-specific differences were identified. A minor part of Giardia ESPs had signal peptides (29% for both isolates) and extracellular vesicles were detected in the ESPs fractions, suggesting alternative secretory pathways. Microscopic analyses showed ESPs binding to IECs and partial internalization. Parasite ESPs reduced ERK1/2 and P38 phosphorylation and NF-κB nuclear translocation. Giardia ESPs altered gene expression in IECs, with a transcriptional profile indicating recruitment of immune cells via chemokines, disturbances in glucose homeostasis, cholesterol and lipid metabolism, cell cycle and induction of apoptosis. CONCLUSIONS:This is the first study identifying Giardia ESPs and evaluating their effects on IECs. It highlights the importance of host and parasite ESPs during interactions and reveals the intricate cellular responses that can explain disease mechanisms and attenuated inflammatory responses during giardiasis. |
| first_indexed | 2024-04-14T05:21:16Z |
| format | Article |
| id | doaj.art-23d3933b256048798e1ca45a77863f6d |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-04-14T05:21:16Z |
| publishDate | 2017-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-23d3933b256048798e1ca45a77863f6d2022-12-22T02:10:11ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352017-12-011112e000612010.1371/journal.pntd.0006120Characterization of the Giardia intestinalis secretome during interaction with human intestinal epithelial cells: The impact on host cells.Showgy Y Ma'ayehJingyi LiuDimitra PeirasmakiKatarina HörnaeusSara Bergström LindManfred GrabherrJonas BergquistStaffan G SvärdBACKGROUND:Giardia intestinalis is a non-invasive protozoan parasite that causes giardiasis in humans, the most common form of parasite-induced diarrhea. Disease mechanisms are not completely defined and very few virulence factors are known. METHODOLOGY:To identify putative virulence factors and elucidate mechanistic pathways leading to disease, we have used proteomics to identify the major excretory-secretory products (ESPs) when Giardia trophozoites of WB and GS isolates (assemblages A and B, respectively) interact with intestinal epithelial cells (IECs) in vitro. FINDINGS:The main parts of the IEC and parasite secretomes are constitutively released proteins, the majority of which are associated with metabolism but several proteins are released in response to their interaction (87 and 41 WB and GS proteins, respectively, 76 and 45 human proteins in response to the respective isolates). In parasitized IECs, the secretome profile indicated effects on the cell actin cytoskeleton and the induction of immune responses whereas that of Giardia showed anti-oxidation, proteolysis (protease-associated) and induction of encystation responses. The Giardia secretome also contained immunodominant and glycosylated proteins as well as new candidate virulence factors and assemblage-specific differences were identified. A minor part of Giardia ESPs had signal peptides (29% for both isolates) and extracellular vesicles were detected in the ESPs fractions, suggesting alternative secretory pathways. Microscopic analyses showed ESPs binding to IECs and partial internalization. Parasite ESPs reduced ERK1/2 and P38 phosphorylation and NF-κB nuclear translocation. Giardia ESPs altered gene expression in IECs, with a transcriptional profile indicating recruitment of immune cells via chemokines, disturbances in glucose homeostasis, cholesterol and lipid metabolism, cell cycle and induction of apoptosis. CONCLUSIONS:This is the first study identifying Giardia ESPs and evaluating their effects on IECs. It highlights the importance of host and parasite ESPs during interactions and reveals the intricate cellular responses that can explain disease mechanisms and attenuated inflammatory responses during giardiasis.http://europepmc.org/articles/PMC5739509?pdf=render |
| spellingShingle | Showgy Y Ma'ayeh Jingyi Liu Dimitra Peirasmaki Katarina Hörnaeus Sara Bergström Lind Manfred Grabherr Jonas Bergquist Staffan G Svärd Characterization of the Giardia intestinalis secretome during interaction with human intestinal epithelial cells: The impact on host cells. PLoS Neglected Tropical Diseases |
| title | Characterization of the Giardia intestinalis secretome during interaction with human intestinal epithelial cells: The impact on host cells. |
| title_full | Characterization of the Giardia intestinalis secretome during interaction with human intestinal epithelial cells: The impact on host cells. |
| title_fullStr | Characterization of the Giardia intestinalis secretome during interaction with human intestinal epithelial cells: The impact on host cells. |
| title_full_unstemmed | Characterization of the Giardia intestinalis secretome during interaction with human intestinal epithelial cells: The impact on host cells. |
| title_short | Characterization of the Giardia intestinalis secretome during interaction with human intestinal epithelial cells: The impact on host cells. |
| title_sort | characterization of the giardia intestinalis secretome during interaction with human intestinal epithelial cells the impact on host cells |
| url | http://europepmc.org/articles/PMC5739509?pdf=render |
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