A Trypanosoma brucei kinesin heavy chain promotes parasite growth by triggering host arginase activity.
In order to promote infection, the blood-borne parasite Trypanosoma brucei releases factors that upregulate arginase expression and activity in myeloid cells.By screening a cDNA library of T. brucei with an antibody neutralizing the arginase-inducing activity of parasite released factors, we identif...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-10-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC3814429?pdf=render |
| _version_ | 1811259411452133376 |
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| author | Géraldine De Muylder Sylvie Daulouède Laurence Lecordier Pierrick Uzureau Yannick Morias Jan Van Den Abbeele Guy Caljon Michel Hérin Philippe Holzmuller Silla Semballa Pierrette Courtois Luc Vanhamme Benoît Stijlemans Patrick De Baetselier Michael P Barrett Jillian L Barlow Andrew N J McKenzie Luke Barron Thomas A Wynn Alain Beschin Philippe Vincendeau Etienne Pays |
| author_facet | Géraldine De Muylder Sylvie Daulouède Laurence Lecordier Pierrick Uzureau Yannick Morias Jan Van Den Abbeele Guy Caljon Michel Hérin Philippe Holzmuller Silla Semballa Pierrette Courtois Luc Vanhamme Benoît Stijlemans Patrick De Baetselier Michael P Barrett Jillian L Barlow Andrew N J McKenzie Luke Barron Thomas A Wynn Alain Beschin Philippe Vincendeau Etienne Pays |
| author_sort | Géraldine De Muylder |
| collection | DOAJ |
| description | In order to promote infection, the blood-borne parasite Trypanosoma brucei releases factors that upregulate arginase expression and activity in myeloid cells.By screening a cDNA library of T. brucei with an antibody neutralizing the arginase-inducing activity of parasite released factors, we identified a Kinesin Heavy Chain isoform, termed TbKHC1, as responsible for this effect. Following interaction with mouse myeloid cells, natural or recombinant TbKHC1 triggered SIGN-R1 receptor-dependent induction of IL-10 production, resulting in arginase-1 activation concomitant with reduction of nitric oxide (NO) synthase activity. This TbKHC1 activity was IL-4Rα-independent and did not mirror M2 activation of myeloid cells. As compared to wild-type T. brucei, infection by TbKHC1 KO parasites was characterized by strongly reduced parasitaemia and prolonged host survival time. By treating infected mice with ornithine or with NO synthase inhibitor, we observed that during the first wave of parasitaemia the parasite growth-promoting effect of TbKHC1-mediated arginase activation resulted more from increased polyamine production than from reduction of NO synthesis. In late stage infection, TbKHC1-mediated reduction of NO synthesis appeared to contribute to liver damage linked to shortening of host survival time.A kinesin heavy chain released by T. brucei induces IL-10 and arginase-1 through SIGN-R1 signaling in myeloid cells, which promotes early trypanosome growth and favors parasite settlement in the host. Moreover, in the late stage of infection, the inhibition of NO synthesis by TbKHC1 contributes to liver pathogenicity. |
| first_indexed | 2024-04-12T18:31:00Z |
| format | Article |
| id | doaj.art-511927836da54f7db78eab97bcc2f4c0 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-04-12T18:31:00Z |
| publishDate | 2013-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-511927836da54f7db78eab97bcc2f4c02022-12-22T03:21:05ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742013-10-01910e100373110.1371/journal.ppat.1003731A Trypanosoma brucei kinesin heavy chain promotes parasite growth by triggering host arginase activity.Géraldine De MuylderSylvie DaulouèdeLaurence LecordierPierrick UzureauYannick MoriasJan Van Den AbbeeleGuy CaljonMichel HérinPhilippe HolzmullerSilla SemballaPierrette CourtoisLuc VanhammeBenoît StijlemansPatrick De BaetselierMichael P BarrettJillian L BarlowAndrew N J McKenzieLuke BarronThomas A WynnAlain BeschinPhilippe VincendeauEtienne PaysIn order to promote infection, the blood-borne parasite Trypanosoma brucei releases factors that upregulate arginase expression and activity in myeloid cells.By screening a cDNA library of T. brucei with an antibody neutralizing the arginase-inducing activity of parasite released factors, we identified a Kinesin Heavy Chain isoform, termed TbKHC1, as responsible for this effect. Following interaction with mouse myeloid cells, natural or recombinant TbKHC1 triggered SIGN-R1 receptor-dependent induction of IL-10 production, resulting in arginase-1 activation concomitant with reduction of nitric oxide (NO) synthase activity. This TbKHC1 activity was IL-4Rα-independent and did not mirror M2 activation of myeloid cells. As compared to wild-type T. brucei, infection by TbKHC1 KO parasites was characterized by strongly reduced parasitaemia and prolonged host survival time. By treating infected mice with ornithine or with NO synthase inhibitor, we observed that during the first wave of parasitaemia the parasite growth-promoting effect of TbKHC1-mediated arginase activation resulted more from increased polyamine production than from reduction of NO synthesis. In late stage infection, TbKHC1-mediated reduction of NO synthesis appeared to contribute to liver damage linked to shortening of host survival time.A kinesin heavy chain released by T. brucei induces IL-10 and arginase-1 through SIGN-R1 signaling in myeloid cells, which promotes early trypanosome growth and favors parasite settlement in the host. Moreover, in the late stage of infection, the inhibition of NO synthesis by TbKHC1 contributes to liver pathogenicity.http://europepmc.org/articles/PMC3814429?pdf=render |
| spellingShingle | Géraldine De Muylder Sylvie Daulouède Laurence Lecordier Pierrick Uzureau Yannick Morias Jan Van Den Abbeele Guy Caljon Michel Hérin Philippe Holzmuller Silla Semballa Pierrette Courtois Luc Vanhamme Benoît Stijlemans Patrick De Baetselier Michael P Barrett Jillian L Barlow Andrew N J McKenzie Luke Barron Thomas A Wynn Alain Beschin Philippe Vincendeau Etienne Pays A Trypanosoma brucei kinesin heavy chain promotes parasite growth by triggering host arginase activity. PLoS Pathogens |
| title | A Trypanosoma brucei kinesin heavy chain promotes parasite growth by triggering host arginase activity. |
| title_full | A Trypanosoma brucei kinesin heavy chain promotes parasite growth by triggering host arginase activity. |
| title_fullStr | A Trypanosoma brucei kinesin heavy chain promotes parasite growth by triggering host arginase activity. |
| title_full_unstemmed | A Trypanosoma brucei kinesin heavy chain promotes parasite growth by triggering host arginase activity. |
| title_short | A Trypanosoma brucei kinesin heavy chain promotes parasite growth by triggering host arginase activity. |
| title_sort | trypanosoma brucei kinesin heavy chain promotes parasite growth by triggering host arginase activity |
| url | http://europepmc.org/articles/PMC3814429?pdf=render |
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