Cargando…
Mannan-Binding Lectin Regulates the Th17/Treg Axis Through JAK/STAT and TGF-β/SMAD Signaling Against Candida albicans Infection
BACKGROUND: Mannan-binding lectin (MBL) is a key molecule in innate immunity and activates the lectin complement pathway, which plays an important role in resisting Candida albicans (C. albicans) infection. However, the underlying mechanism of this resistance to infection remains unclear. METHODS: I...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8923702/ https://www.ncbi.nlm.nih.gov/pubmed/35300210 http://dx.doi.org/10.2147/JIR.S344489 |
_version_ | 1784669714427936768 |
---|---|
author | Wang, Fanping Yang, Yonghui Li, Zhixin Wang, Yan Zhang, Zhenchao Zhang, Wei Mu, Yonghui Yang, Jingwen Yu, Lili Wang, Mingyong |
author_facet | Wang, Fanping Yang, Yonghui Li, Zhixin Wang, Yan Zhang, Zhenchao Zhang, Wei Mu, Yonghui Yang, Jingwen Yu, Lili Wang, Mingyong |
author_sort | Wang, Fanping |
collection | PubMed |
description | BACKGROUND: Mannan-binding lectin (MBL) is a key molecule in innate immunity and activates the lectin complement pathway, which plays an important role in resisting Candida albicans (C. albicans) infection. However, the underlying mechanism of this resistance to infection remains unclear. METHODS: In this study, we investigated how MBL regulates the differentiation of CD4(+) T cells into T helper type 17 (Th17) and T regulatory (Treg) cells against C. albicans in mice, as well as the underlying mechanisms. We generated MBL double-knockout (KO) mice and infected them with C. albicans by intraperitoneal injection. RESULTS: Compared with that in wild-type (WT) mice, the percentage of Th17 cells increased in MBL-null mice, whereas Treg cells decreased, indicating that MBL might regulate the Th17/Treg balance. In addition, in MBL-null mice, the expression levels of interleukin (IL)-17A, IL-21, and the master transcription factor of Th17 cells, RORγt, significantly increased. Conversely, IL-10, IL-2, and the Treg-specific transcription factor, Foxp3, decreased. Moreover, we found that the levels of TGF-β and IL-6 upregulated in MBL-null mice. Mechanistically, we found that MBL regulated the TGF-β/SMAD pathway through the inhibition of p-SMAD2 and promotion of p-SMAD3, and mediated the JAK/STAT pathway through the inhibition of p-JAK2 and p-STAT3 and promotion of p-JAK3 and p-STAT5. MBL double-KO mice showed a more severe inflammatory response and significantly lower survival rates with C. albicans infection. CONCLUSION: These results suggest that MBL regulates the Th17/Treg cell balance to inhibit inflammatory responses, possibly via IL-6- and TGF-β-mediated JAK/STAT and TGF-β/SMAD signaling, and play an important role in anti-C. albicans infection. |
format | Online Article Text |
id | pubmed-8923702 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-89237022022-03-16 Mannan-Binding Lectin Regulates the Th17/Treg Axis Through JAK/STAT and TGF-β/SMAD Signaling Against Candida albicans Infection Wang, Fanping Yang, Yonghui Li, Zhixin Wang, Yan Zhang, Zhenchao Zhang, Wei Mu, Yonghui Yang, Jingwen Yu, Lili Wang, Mingyong J Inflamm Res Original Research BACKGROUND: Mannan-binding lectin (MBL) is a key molecule in innate immunity and activates the lectin complement pathway, which plays an important role in resisting Candida albicans (C. albicans) infection. However, the underlying mechanism of this resistance to infection remains unclear. METHODS: In this study, we investigated how MBL regulates the differentiation of CD4(+) T cells into T helper type 17 (Th17) and T regulatory (Treg) cells against C. albicans in mice, as well as the underlying mechanisms. We generated MBL double-knockout (KO) mice and infected them with C. albicans by intraperitoneal injection. RESULTS: Compared with that in wild-type (WT) mice, the percentage of Th17 cells increased in MBL-null mice, whereas Treg cells decreased, indicating that MBL might regulate the Th17/Treg balance. In addition, in MBL-null mice, the expression levels of interleukin (IL)-17A, IL-21, and the master transcription factor of Th17 cells, RORγt, significantly increased. Conversely, IL-10, IL-2, and the Treg-specific transcription factor, Foxp3, decreased. Moreover, we found that the levels of TGF-β and IL-6 upregulated in MBL-null mice. Mechanistically, we found that MBL regulated the TGF-β/SMAD pathway through the inhibition of p-SMAD2 and promotion of p-SMAD3, and mediated the JAK/STAT pathway through the inhibition of p-JAK2 and p-STAT3 and promotion of p-JAK3 and p-STAT5. MBL double-KO mice showed a more severe inflammatory response and significantly lower survival rates with C. albicans infection. CONCLUSION: These results suggest that MBL regulates the Th17/Treg cell balance to inhibit inflammatory responses, possibly via IL-6- and TGF-β-mediated JAK/STAT and TGF-β/SMAD signaling, and play an important role in anti-C. albicans infection. Dove 2022-03-11 /pmc/articles/PMC8923702/ /pubmed/35300210 http://dx.doi.org/10.2147/JIR.S344489 Text en © 2022 Wang et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Wang, Fanping Yang, Yonghui Li, Zhixin Wang, Yan Zhang, Zhenchao Zhang, Wei Mu, Yonghui Yang, Jingwen Yu, Lili Wang, Mingyong Mannan-Binding Lectin Regulates the Th17/Treg Axis Through JAK/STAT and TGF-β/SMAD Signaling Against Candida albicans Infection |
title | Mannan-Binding Lectin Regulates the Th17/Treg Axis Through JAK/STAT and TGF-β/SMAD Signaling Against Candida albicans Infection |
title_full | Mannan-Binding Lectin Regulates the Th17/Treg Axis Through JAK/STAT and TGF-β/SMAD Signaling Against Candida albicans Infection |
title_fullStr | Mannan-Binding Lectin Regulates the Th17/Treg Axis Through JAK/STAT and TGF-β/SMAD Signaling Against Candida albicans Infection |
title_full_unstemmed | Mannan-Binding Lectin Regulates the Th17/Treg Axis Through JAK/STAT and TGF-β/SMAD Signaling Against Candida albicans Infection |
title_short | Mannan-Binding Lectin Regulates the Th17/Treg Axis Through JAK/STAT and TGF-β/SMAD Signaling Against Candida albicans Infection |
title_sort | mannan-binding lectin regulates the th17/treg axis through jak/stat and tgf-β/smad signaling against candida albicans infection |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8923702/ https://www.ncbi.nlm.nih.gov/pubmed/35300210 http://dx.doi.org/10.2147/JIR.S344489 |
work_keys_str_mv | AT wangfanping mannanbindinglectinregulatestheth17tregaxisthroughjakstatandtgfbsmadsignalingagainstcandidaalbicansinfection AT yangyonghui mannanbindinglectinregulatestheth17tregaxisthroughjakstatandtgfbsmadsignalingagainstcandidaalbicansinfection AT lizhixin mannanbindinglectinregulatestheth17tregaxisthroughjakstatandtgfbsmadsignalingagainstcandidaalbicansinfection AT wangyan mannanbindinglectinregulatestheth17tregaxisthroughjakstatandtgfbsmadsignalingagainstcandidaalbicansinfection AT zhangzhenchao mannanbindinglectinregulatestheth17tregaxisthroughjakstatandtgfbsmadsignalingagainstcandidaalbicansinfection AT zhangwei mannanbindinglectinregulatestheth17tregaxisthroughjakstatandtgfbsmadsignalingagainstcandidaalbicansinfection AT muyonghui mannanbindinglectinregulatestheth17tregaxisthroughjakstatandtgfbsmadsignalingagainstcandidaalbicansinfection AT yangjingwen mannanbindinglectinregulatestheth17tregaxisthroughjakstatandtgfbsmadsignalingagainstcandidaalbicansinfection AT yulili mannanbindinglectinregulatestheth17tregaxisthroughjakstatandtgfbsmadsignalingagainstcandidaalbicansinfection AT wangmingyong mannanbindinglectinregulatestheth17tregaxisthroughjakstatandtgfbsmadsignalingagainstcandidaalbicansinfection |