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TLR7 modulates extramedullary splenic erythropoiesis in P. yoelii NSM-infected mice through the regulation of iron metabolism of macrophages with IFN-γ
Splenomegaly is a prominent clinical manifestation of malaria and the causes remain incompletely clear. Anemia is induced in malaria and extramedullary splenic erythropoiesis is compensation for the loss of erythrocytes. However, the regulation of extramedullary splenic erythropoiesis in malaria is...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10174296/ https://www.ncbi.nlm.nih.gov/pubmed/37180169 http://dx.doi.org/10.3389/fimmu.2023.1123074 |
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author | Li, Jiajie Liu, Lin Xing, Junmin Chen, Dianhui Fang, Chao Mo, Feng Gong, Yumei Tan, Zhengrong Liang, Guikuan Xiao, Wei Tang, Shanni Wei, Haixia Zhao, Shan Xie, Hongyan Pan, Xingfei Yin, Xiaomao Huang, Jun |
author_facet | Li, Jiajie Liu, Lin Xing, Junmin Chen, Dianhui Fang, Chao Mo, Feng Gong, Yumei Tan, Zhengrong Liang, Guikuan Xiao, Wei Tang, Shanni Wei, Haixia Zhao, Shan Xie, Hongyan Pan, Xingfei Yin, Xiaomao Huang, Jun |
author_sort | Li, Jiajie |
collection | PubMed |
description | Splenomegaly is a prominent clinical manifestation of malaria and the causes remain incompletely clear. Anemia is induced in malaria and extramedullary splenic erythropoiesis is compensation for the loss of erythrocytes. However, the regulation of extramedullary splenic erythropoiesis in malaria is unknown. An inflammatory response could facilitate extramedullary splenic erythropoiesis in the settings of infection and inflammation. Here, when mice were infected with rodent parasites, Plasmodium yoelii NSM, TLR7 expression in splenocytes was increased. To explore the roles of TLR7 in splenic erythropoiesis, we infected wild-type and TLR7 (-/-) C57BL/6 mice with P. yoelii NSM and found that the development of splenic erythroid progenitor cells was impeded in TLR7 (-/-) mice. Contrarily, the treatment of the TLR7 agonist, R848, promoted extramedullary splenic erythropoiesis in wild-type infected mice, which highlights the implication of TLR7 on splenic erythropoiesis. Then, we found that TLR7 promoted the production of IFN-γ that could enhance phagocytosis of infected erythrocytes by RAW264.7. After phagocytosis of infected erythrocytes, the iron metabolism of RAW264.7 was upregulated, evidenced by higher iron content and expression of Hmox1 and Slc40a1. Additionally, the neutralization of IFN-γ impeded the extramedullary splenic erythropoiesis modestly and reduced the iron accumulation in the spleen of infected mice. In conclusion, TLR7 promoted extramedullary splenic erythropoiesis in P. yoelii NSM-infected mice. TLR7 enhanced the production of IFN-γ, and IFN-γ promoted phagocytosis of infected erythrocytes and the iron metabolism of macrophages in vitro, which may be related to the regulation of extramedullary splenic erythropoiesis by TLR7. |
format | Online Article Text |
id | pubmed-10174296 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101742962023-05-12 TLR7 modulates extramedullary splenic erythropoiesis in P. yoelii NSM-infected mice through the regulation of iron metabolism of macrophages with IFN-γ Li, Jiajie Liu, Lin Xing, Junmin Chen, Dianhui Fang, Chao Mo, Feng Gong, Yumei Tan, Zhengrong Liang, Guikuan Xiao, Wei Tang, Shanni Wei, Haixia Zhao, Shan Xie, Hongyan Pan, Xingfei Yin, Xiaomao Huang, Jun Front Immunol Immunology Splenomegaly is a prominent clinical manifestation of malaria and the causes remain incompletely clear. Anemia is induced in malaria and extramedullary splenic erythropoiesis is compensation for the loss of erythrocytes. However, the regulation of extramedullary splenic erythropoiesis in malaria is unknown. An inflammatory response could facilitate extramedullary splenic erythropoiesis in the settings of infection and inflammation. Here, when mice were infected with rodent parasites, Plasmodium yoelii NSM, TLR7 expression in splenocytes was increased. To explore the roles of TLR7 in splenic erythropoiesis, we infected wild-type and TLR7 (-/-) C57BL/6 mice with P. yoelii NSM and found that the development of splenic erythroid progenitor cells was impeded in TLR7 (-/-) mice. Contrarily, the treatment of the TLR7 agonist, R848, promoted extramedullary splenic erythropoiesis in wild-type infected mice, which highlights the implication of TLR7 on splenic erythropoiesis. Then, we found that TLR7 promoted the production of IFN-γ that could enhance phagocytosis of infected erythrocytes by RAW264.7. After phagocytosis of infected erythrocytes, the iron metabolism of RAW264.7 was upregulated, evidenced by higher iron content and expression of Hmox1 and Slc40a1. Additionally, the neutralization of IFN-γ impeded the extramedullary splenic erythropoiesis modestly and reduced the iron accumulation in the spleen of infected mice. In conclusion, TLR7 promoted extramedullary splenic erythropoiesis in P. yoelii NSM-infected mice. TLR7 enhanced the production of IFN-γ, and IFN-γ promoted phagocytosis of infected erythrocytes and the iron metabolism of macrophages in vitro, which may be related to the regulation of extramedullary splenic erythropoiesis by TLR7. Frontiers Media S.A. 2023-04-27 /pmc/articles/PMC10174296/ /pubmed/37180169 http://dx.doi.org/10.3389/fimmu.2023.1123074 Text en Copyright © 2023 Li, Liu, Xing, Chen, Fang, Mo, Gong, Tan, Liang, Xiao, Tang, Wei, Zhao, Xie, Pan, Yin and Huang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Li, Jiajie Liu, Lin Xing, Junmin Chen, Dianhui Fang, Chao Mo, Feng Gong, Yumei Tan, Zhengrong Liang, Guikuan Xiao, Wei Tang, Shanni Wei, Haixia Zhao, Shan Xie, Hongyan Pan, Xingfei Yin, Xiaomao Huang, Jun TLR7 modulates extramedullary splenic erythropoiesis in P. yoelii NSM-infected mice through the regulation of iron metabolism of macrophages with IFN-γ |
title | TLR7 modulates extramedullary splenic erythropoiesis in P. yoelii NSM-infected mice through the regulation of iron metabolism of macrophages with IFN-γ |
title_full | TLR7 modulates extramedullary splenic erythropoiesis in P. yoelii NSM-infected mice through the regulation of iron metabolism of macrophages with IFN-γ |
title_fullStr | TLR7 modulates extramedullary splenic erythropoiesis in P. yoelii NSM-infected mice through the regulation of iron metabolism of macrophages with IFN-γ |
title_full_unstemmed | TLR7 modulates extramedullary splenic erythropoiesis in P. yoelii NSM-infected mice through the regulation of iron metabolism of macrophages with IFN-γ |
title_short | TLR7 modulates extramedullary splenic erythropoiesis in P. yoelii NSM-infected mice through the regulation of iron metabolism of macrophages with IFN-γ |
title_sort | tlr7 modulates extramedullary splenic erythropoiesis in p. yoelii nsm-infected mice through the regulation of iron metabolism of macrophages with ifn-γ |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10174296/ https://www.ncbi.nlm.nih.gov/pubmed/37180169 http://dx.doi.org/10.3389/fimmu.2023.1123074 |
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