IRF-5 Expression in Myeloid Cells Is Required for Splenomegaly in L. donovani Infected Mice
Persistent Leishmania donovani infection is characterized by chronic inflammation, immune suppression, and splenomegaly. We have previously reported that the transcription factor interferon regulatory factor 5 (IRF-5) is largely responsible for inducing the inflammatory response and maintaining prot...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.03071/full |
| _version_ | 1818509514015506432 |
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| author | Linh Thuy Mai Mélina Smans Sasha Silva-Barrios Aymeric Fabié Simona Stäger |
| author_facet | Linh Thuy Mai Mélina Smans Sasha Silva-Barrios Aymeric Fabié Simona Stäger |
| author_sort | Linh Thuy Mai |
| collection | DOAJ |
| description | Persistent Leishmania donovani infection is characterized by chronic inflammation, immune suppression, and splenomegaly. We have previously reported that the transcription factor interferon regulatory factor 5 (IRF-5) is largely responsible for inducing the inflammatory response and maintaining protective Th1 cells following L. donovani inoculation in mice. However, the cellular source responsible for these effects is yet unknown. In this study, we investigated the role of IRF-5 in myeloid cells during experimental visceral leishmaniasis (VL). First, we show that the LysM-Cre mouse model is not suited for investigating gene expression in splenic myeloid cells during experimental VL. Using the Cd11c-Cre mouse model, we demonstrate that Irf5 expression in CD11c+ cells (monocytes, dendritic cells, activated macrophages) is essential for inducing splenomegaly and for recruiting myeloid cells to the spleen, but it is not required for the development or maintenance of parasite-specific IFNγ-producing CD4 T cells. CD11c-specific Irf5−/− mice are more resistant to L. donovani infection, suggesting that the induction of splenomegaly is detrimental to the host. |
| first_indexed | 2024-12-10T22:46:29Z |
| format | Article |
| id | doaj.art-d3ac95650e96431e8d151f2e8586559c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T22:46:29Z |
| publishDate | 2020-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d3ac95650e96431e8d151f2e8586559c2022-12-22T01:30:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-01-011010.3389/fimmu.2019.03071497668IRF-5 Expression in Myeloid Cells Is Required for Splenomegaly in L. donovani Infected MiceLinh Thuy MaiMélina SmansSasha Silva-BarriosAymeric FabiéSimona StägerPersistent Leishmania donovani infection is characterized by chronic inflammation, immune suppression, and splenomegaly. We have previously reported that the transcription factor interferon regulatory factor 5 (IRF-5) is largely responsible for inducing the inflammatory response and maintaining protective Th1 cells following L. donovani inoculation in mice. However, the cellular source responsible for these effects is yet unknown. In this study, we investigated the role of IRF-5 in myeloid cells during experimental visceral leishmaniasis (VL). First, we show that the LysM-Cre mouse model is not suited for investigating gene expression in splenic myeloid cells during experimental VL. Using the Cd11c-Cre mouse model, we demonstrate that Irf5 expression in CD11c+ cells (monocytes, dendritic cells, activated macrophages) is essential for inducing splenomegaly and for recruiting myeloid cells to the spleen, but it is not required for the development or maintenance of parasite-specific IFNγ-producing CD4 T cells. CD11c-specific Irf5−/− mice are more resistant to L. donovani infection, suggesting that the induction of splenomegaly is detrimental to the host.https://www.frontiersin.org/article/10.3389/fimmu.2019.03071/fullLeishmaniaIRF5myeloid cellssplenomegalyTh1LysM-cre |
| spellingShingle | Linh Thuy Mai Mélina Smans Sasha Silva-Barrios Aymeric Fabié Simona Stäger IRF-5 Expression in Myeloid Cells Is Required for Splenomegaly in L. donovani Infected Mice Frontiers in Immunology Leishmania IRF5 myeloid cells splenomegaly Th1 LysM-cre |
| title | IRF-5 Expression in Myeloid Cells Is Required for Splenomegaly in L. donovani Infected Mice |
| title_full | IRF-5 Expression in Myeloid Cells Is Required for Splenomegaly in L. donovani Infected Mice |
| title_fullStr | IRF-5 Expression in Myeloid Cells Is Required for Splenomegaly in L. donovani Infected Mice |
| title_full_unstemmed | IRF-5 Expression in Myeloid Cells Is Required for Splenomegaly in L. donovani Infected Mice |
| title_short | IRF-5 Expression in Myeloid Cells Is Required for Splenomegaly in L. donovani Infected Mice |
| title_sort | irf 5 expression in myeloid cells is required for splenomegaly in l donovani infected mice |
| topic | Leishmania IRF5 myeloid cells splenomegaly Th1 LysM-cre |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.03071/full |
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