Upregulation of retinal dehydrogenase 2 in alternatively activated macrophages during retinoid-dependent type-2 immunity to helminth infection in mice.
Although the vitamin A metabolite retinoic acid (RA) plays a critical role in immune function, RA synthesis during infection is poorly understood. Here, we show that retinal dehydrogenases (Raldh), required for the synthesis of RA, are induced during a retinoid-dependent type-2 immune response elici...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002883&type=printable |
| _version_ | 1826799366908674048 |
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| author | Mara J Broadhurst Jacqueline M Leung K C Lim Natasha M Girgis Uma Mahesh Gundra Padraic G Fallon Mary Premenko-Lanier James H McKerrow Joseph M McCune P'ng Loke |
| author_facet | Mara J Broadhurst Jacqueline M Leung K C Lim Natasha M Girgis Uma Mahesh Gundra Padraic G Fallon Mary Premenko-Lanier James H McKerrow Joseph M McCune P'ng Loke |
| author_sort | Mara J Broadhurst |
| collection | DOAJ |
| description | Although the vitamin A metabolite retinoic acid (RA) plays a critical role in immune function, RA synthesis during infection is poorly understood. Here, we show that retinal dehydrogenases (Raldh), required for the synthesis of RA, are induced during a retinoid-dependent type-2 immune response elicited by Schistosoma mansoni infection, but not during a retinoid-independent anti-viral immune response. Vitamin A deficient mice have a selective defect in T(H)2 responses to S. mansoni, but retained normal LCMV specific T(H)1 responses. A combination of in situ imaging, intra-vital imaging, and sort purification revealed that alternatively activated macrophages (AAMφ) express high levels of Raldh2 during S. mansoni infection. IL-4 induces Raldh2 expression in bone marrow-derived macrophages in vitro and peritoneal macrophages in vivo. Finally, in vivo derived AAMφ have an enhanced capacity to induce Foxp3 expression in CD4+ cells through an RA dependent mechanism, especially in combination with TGF-β. The regulation of Raldh enzymes during infection is pathogen specific and reflects differential requirements for RA during effector responses. Specifically, AAMφ are an inducible source of RA synthesis during helminth infections and T(H)2 responses that may be important in regulating immune responses. |
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| format | Article |
| id | doaj.art-c974b41c7fcf44488aacbcb00422af1a |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2025-03-17T00:33:57Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-c974b41c7fcf44488aacbcb00422af1a2025-02-21T05:33:11ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742012-01-0188e100288310.1371/journal.ppat.1002883Upregulation of retinal dehydrogenase 2 in alternatively activated macrophages during retinoid-dependent type-2 immunity to helminth infection in mice.Mara J BroadhurstJacqueline M LeungK C LimNatasha M GirgisUma Mahesh GundraPadraic G FallonMary Premenko-LanierJames H McKerrowJoseph M McCuneP'ng LokeAlthough the vitamin A metabolite retinoic acid (RA) plays a critical role in immune function, RA synthesis during infection is poorly understood. Here, we show that retinal dehydrogenases (Raldh), required for the synthesis of RA, are induced during a retinoid-dependent type-2 immune response elicited by Schistosoma mansoni infection, but not during a retinoid-independent anti-viral immune response. Vitamin A deficient mice have a selective defect in T(H)2 responses to S. mansoni, but retained normal LCMV specific T(H)1 responses. A combination of in situ imaging, intra-vital imaging, and sort purification revealed that alternatively activated macrophages (AAMφ) express high levels of Raldh2 during S. mansoni infection. IL-4 induces Raldh2 expression in bone marrow-derived macrophages in vitro and peritoneal macrophages in vivo. Finally, in vivo derived AAMφ have an enhanced capacity to induce Foxp3 expression in CD4+ cells through an RA dependent mechanism, especially in combination with TGF-β. The regulation of Raldh enzymes during infection is pathogen specific and reflects differential requirements for RA during effector responses. Specifically, AAMφ are an inducible source of RA synthesis during helminth infections and T(H)2 responses that may be important in regulating immune responses.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002883&type=printable |
| spellingShingle | Mara J Broadhurst Jacqueline M Leung K C Lim Natasha M Girgis Uma Mahesh Gundra Padraic G Fallon Mary Premenko-Lanier James H McKerrow Joseph M McCune P'ng Loke Upregulation of retinal dehydrogenase 2 in alternatively activated macrophages during retinoid-dependent type-2 immunity to helminth infection in mice. PLoS Pathogens |
| title | Upregulation of retinal dehydrogenase 2 in alternatively activated macrophages during retinoid-dependent type-2 immunity to helminth infection in mice. |
| title_full | Upregulation of retinal dehydrogenase 2 in alternatively activated macrophages during retinoid-dependent type-2 immunity to helminth infection in mice. |
| title_fullStr | Upregulation of retinal dehydrogenase 2 in alternatively activated macrophages during retinoid-dependent type-2 immunity to helminth infection in mice. |
| title_full_unstemmed | Upregulation of retinal dehydrogenase 2 in alternatively activated macrophages during retinoid-dependent type-2 immunity to helminth infection in mice. |
| title_short | Upregulation of retinal dehydrogenase 2 in alternatively activated macrophages during retinoid-dependent type-2 immunity to helminth infection in mice. |
| title_sort | upregulation of retinal dehydrogenase 2 in alternatively activated macrophages during retinoid dependent type 2 immunity to helminth infection in mice |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002883&type=printable |
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