H-IPSE is a pathogen-secreted host nucleus infiltrating protein (infiltrin) expressed exclusively by the Schistosoma haematobium egg stage
Urogenital schistosomiasis, caused by the parasitic trematode Schistosoma haematobium, affects over 112 million people worldwide. As with S. mansoni infections, the pathology in urogenital schistosomiasis is mainly related to the egg stage, which induces granulomatous inflammation of affected tissue...
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| Format: | Article |
| Language: | English |
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ASM Press
2017
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| Online Access: | https://eprints.nottingham.ac.uk/46583/ |
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| author | Pennington, Luke F. Alouffi, Abdulaziz Mbanefo, Evaristus C. Ray, Debalina Heery, David M. Jardetzky, Theodore S. Hsieh, Michael H. Falcone, Franco H. |
| author_facet | Pennington, Luke F. Alouffi, Abdulaziz Mbanefo, Evaristus C. Ray, Debalina Heery, David M. Jardetzky, Theodore S. Hsieh, Michael H. Falcone, Franco H. |
| author_sort | Pennington, Luke F. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Urogenital schistosomiasis, caused by the parasitic trematode Schistosoma haematobium, affects over 112 million people worldwide. As with S. mansoni infections, the pathology in urogenital schistosomiasis is mainly related to the egg stage, which induces granulomatous inflammation of affected tissues. Schistosoma eggs and their secretions have been studied extensively for the related S. mansoni organism which is more amenable to laboratory studies. Indeed, we have shown that IPSE/alpha-1 (M-IPSE herein), a major protein secreted from S .mansoni eggs, can infiltrate host cells. Although M-IPSE function is unknown, its ability to translocate to their nucleus and bind DNA suggests a possible role in immune modulation of host cell tissues. Whether IPSE homologs are expressed in other Schistosome species has not been investigated.
Here, we describe the cloning of two paralog genes H03-IPSE and H06-IPSE which are the ortholog of M-IPSE, from the egg-cDNA of S. haematobium. Using PCR and immunodetection, we confirmed that expression of these genes is restricted to the egg stage and female adult worms, while H-IPSE protein is only detectable in mature eggs but not adults. We show that both H03-IPSE and H06-IPSE proteins can infiltrate HTB-9 bladder cells when added exogenously to culture medium. Monopartite C-terminal NLS motifs conserved in H03-IPSE ‘SKRRRKY’ and H06-IPSE ‘SKRGRKY’ NLS motifs, are responsible for targeting the proteins to the nucleus of HTB-9 cells, as demonstrated by site directed mutagenesis and GFP tagging. Thus, S. haematobium eggs express IPSE homologs that appear to perform similar functions in infiltrating host cells. |
| first_indexed | 2025-11-14T20:02:38Z |
| format | Article |
| id | nottingham-46583 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T20:02:38Z |
| publishDate | 2017 |
| publisher | ASM Press |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-465832017-11-24T12:37:02Z https://eprints.nottingham.ac.uk/46583/ H-IPSE is a pathogen-secreted host nucleus infiltrating protein (infiltrin) expressed exclusively by the Schistosoma haematobium egg stage Pennington, Luke F. Alouffi, Abdulaziz Mbanefo, Evaristus C. Ray, Debalina Heery, David M. Jardetzky, Theodore S. Hsieh, Michael H. Falcone, Franco H. Urogenital schistosomiasis, caused by the parasitic trematode Schistosoma haematobium, affects over 112 million people worldwide. As with S. mansoni infections, the pathology in urogenital schistosomiasis is mainly related to the egg stage, which induces granulomatous inflammation of affected tissues. Schistosoma eggs and their secretions have been studied extensively for the related S. mansoni organism which is more amenable to laboratory studies. Indeed, we have shown that IPSE/alpha-1 (M-IPSE herein), a major protein secreted from S .mansoni eggs, can infiltrate host cells. Although M-IPSE function is unknown, its ability to translocate to their nucleus and bind DNA suggests a possible role in immune modulation of host cell tissues. Whether IPSE homologs are expressed in other Schistosome species has not been investigated. Here, we describe the cloning of two paralog genes H03-IPSE and H06-IPSE which are the ortholog of M-IPSE, from the egg-cDNA of S. haematobium. Using PCR and immunodetection, we confirmed that expression of these genes is restricted to the egg stage and female adult worms, while H-IPSE protein is only detectable in mature eggs but not adults. We show that both H03-IPSE and H06-IPSE proteins can infiltrate HTB-9 bladder cells when added exogenously to culture medium. Monopartite C-terminal NLS motifs conserved in H03-IPSE ‘SKRRRKY’ and H06-IPSE ‘SKRGRKY’ NLS motifs, are responsible for targeting the proteins to the nucleus of HTB-9 cells, as demonstrated by site directed mutagenesis and GFP tagging. Thus, S. haematobium eggs express IPSE homologs that appear to perform similar functions in infiltrating host cells. ASM Press 2017-12-31 Article PeerReviewed application/pdf en cc_by https://eprints.nottingham.ac.uk/46583/10/Infect.%20Immun.-2017-Pennington-.pdf Pennington, Luke F., Alouffi, Abdulaziz, Mbanefo, Evaristus C., Ray, Debalina, Heery, David M., Jardetzky, Theodore S., Hsieh, Michael H. and Falcone, Franco H. (2017) H-IPSE is a pathogen-secreted host nucleus infiltrating protein (infiltrin) expressed exclusively by the Schistosoma haematobium egg stage. Infection and Immunity, 85 (12). e00301-17/1. ISSN 1098-5522 Schistosoma haematobium; Nuclear localization signal; Schistosomiasis http://iai.asm.org/content/85/12/e00301-17 doi:10.1128/IAI.00301-17 doi:10.1128/IAI.00301-17 |
| spellingShingle | Schistosoma haematobium; Nuclear localization signal; Schistosomiasis Pennington, Luke F. Alouffi, Abdulaziz Mbanefo, Evaristus C. Ray, Debalina Heery, David M. Jardetzky, Theodore S. Hsieh, Michael H. Falcone, Franco H. H-IPSE is a pathogen-secreted host nucleus infiltrating protein (infiltrin) expressed exclusively by the Schistosoma haematobium egg stage |
| title | H-IPSE is a pathogen-secreted host nucleus infiltrating protein (infiltrin) expressed exclusively by the Schistosoma haematobium egg stage |
| title_full | H-IPSE is a pathogen-secreted host nucleus infiltrating protein (infiltrin) expressed exclusively by the Schistosoma haematobium egg stage |
| title_fullStr | H-IPSE is a pathogen-secreted host nucleus infiltrating protein (infiltrin) expressed exclusively by the Schistosoma haematobium egg stage |
| title_full_unstemmed | H-IPSE is a pathogen-secreted host nucleus infiltrating protein (infiltrin) expressed exclusively by the Schistosoma haematobium egg stage |
| title_short | H-IPSE is a pathogen-secreted host nucleus infiltrating protein (infiltrin) expressed exclusively by the Schistosoma haematobium egg stage |
| title_sort | h-ipse is a pathogen-secreted host nucleus infiltrating protein (infiltrin) expressed exclusively by the schistosoma haematobium egg stage |
| topic | Schistosoma haematobium; Nuclear localization signal; Schistosomiasis |
| url | https://eprints.nottingham.ac.uk/46583/ https://eprints.nottingham.ac.uk/46583/ https://eprints.nottingham.ac.uk/46583/ |