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SHP-2 Mediates Cryptosporidium parvum Infectivity in Human Intestinal Epithelial Cells
The parasite, Cryptosporidium parvum, induces human gastroenteritis through infection of host epithelial cells in the small intestine. During the initial stage of infection, C. parvum is reported to engage host mechanisms at the host cell-parasite interface to form a parasitophorous vacuole. We dete...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640876/ https://www.ncbi.nlm.nih.gov/pubmed/26556238 http://dx.doi.org/10.1371/journal.pone.0142219 |
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author | Varughese, Eunice A. Kasper, Susan Anneken, Emily M. Yadav, Jagjit S. |
author_facet | Varughese, Eunice A. Kasper, Susan Anneken, Emily M. Yadav, Jagjit S. |
author_sort | Varughese, Eunice A. |
collection | PubMed |
description | The parasite, Cryptosporidium parvum, induces human gastroenteritis through infection of host epithelial cells in the small intestine. During the initial stage of infection, C. parvum is reported to engage host mechanisms at the host cell-parasite interface to form a parasitophorous vacuole. We determined that upon infection, the larger molecular weight proteins in human small intestinal epithelial host cells (FHs 74 Int) appeared to globally undergo tyrosine dephosphorylation. In parallel, expression of the cytoplasmic protein tyrosine phosphatase Src homology-2 domain-containing phosphatase 2 (SHP-2) increased in a time-dependent manner. SHP-2 co-localized with the C. parvum sporozoite and this interaction increased the rate of C. parvum infectivity through SH2-mediated SHP-2 activity. Furthermore, we show that one potential target that SHP-2 acts upon is the focal adhesion protein, paxillin, which undergoes moderate dephosphorylation following infection, with inhibition of SHP-2 rescuing paxillin phosphorylation. Importantly, treatment with an inhibitor to SHP-2 and with an inhibitor to paxillin and Src family kinases, effectively decreased the multiplicity of C. parvum infection in a dose-dependent manner. Thus, our study reveals an important role for SHP-2 in the pathogenesis of C. parvum. Furthermore, while host proteins can be recruited to participate in the development of the electron dense band at the host cell-parasite interface, our study implies for the first time that SHP-2 appears to be recruited by the C. parvum sporozoite to regulate infectivity. Taken together, these findings suggest that SHP-2 and its down-stream target paxillin could serve as targets for intervention. |
format | Online Article Text |
id | pubmed-4640876 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-46408762015-11-13 SHP-2 Mediates Cryptosporidium parvum Infectivity in Human Intestinal Epithelial Cells Varughese, Eunice A. Kasper, Susan Anneken, Emily M. Yadav, Jagjit S. PLoS One Research Article The parasite, Cryptosporidium parvum, induces human gastroenteritis through infection of host epithelial cells in the small intestine. During the initial stage of infection, C. parvum is reported to engage host mechanisms at the host cell-parasite interface to form a parasitophorous vacuole. We determined that upon infection, the larger molecular weight proteins in human small intestinal epithelial host cells (FHs 74 Int) appeared to globally undergo tyrosine dephosphorylation. In parallel, expression of the cytoplasmic protein tyrosine phosphatase Src homology-2 domain-containing phosphatase 2 (SHP-2) increased in a time-dependent manner. SHP-2 co-localized with the C. parvum sporozoite and this interaction increased the rate of C. parvum infectivity through SH2-mediated SHP-2 activity. Furthermore, we show that one potential target that SHP-2 acts upon is the focal adhesion protein, paxillin, which undergoes moderate dephosphorylation following infection, with inhibition of SHP-2 rescuing paxillin phosphorylation. Importantly, treatment with an inhibitor to SHP-2 and with an inhibitor to paxillin and Src family kinases, effectively decreased the multiplicity of C. parvum infection in a dose-dependent manner. Thus, our study reveals an important role for SHP-2 in the pathogenesis of C. parvum. Furthermore, while host proteins can be recruited to participate in the development of the electron dense band at the host cell-parasite interface, our study implies for the first time that SHP-2 appears to be recruited by the C. parvum sporozoite to regulate infectivity. Taken together, these findings suggest that SHP-2 and its down-stream target paxillin could serve as targets for intervention. Public Library of Science 2015-11-10 /pmc/articles/PMC4640876/ /pubmed/26556238 http://dx.doi.org/10.1371/journal.pone.0142219 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Varughese, Eunice A. Kasper, Susan Anneken, Emily M. Yadav, Jagjit S. SHP-2 Mediates Cryptosporidium parvum Infectivity in Human Intestinal Epithelial Cells |
title | SHP-2 Mediates Cryptosporidium parvum Infectivity in Human Intestinal Epithelial Cells |
title_full | SHP-2 Mediates Cryptosporidium parvum Infectivity in Human Intestinal Epithelial Cells |
title_fullStr | SHP-2 Mediates Cryptosporidium parvum Infectivity in Human Intestinal Epithelial Cells |
title_full_unstemmed | SHP-2 Mediates Cryptosporidium parvum Infectivity in Human Intestinal Epithelial Cells |
title_short | SHP-2 Mediates Cryptosporidium parvum Infectivity in Human Intestinal Epithelial Cells |
title_sort | shp-2 mediates cryptosporidium parvum infectivity in human intestinal epithelial cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640876/ https://www.ncbi.nlm.nih.gov/pubmed/26556238 http://dx.doi.org/10.1371/journal.pone.0142219 |
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