Proline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to development of allergic asthma in childhood of mice
BackgroundInfants with respiratory syncytial virus (RSV)-associated bronchiolitis are at increased risk of childhood asthma. Recent studies demonstrated that certain infections induce innate immune memory (also termed trained immunity), especially in macrophages, to respond more strongly to future s...
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| Format: | Article |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.977235/full |
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| author | Hanglin Li Linyan Ma Wenjian Li Wenjian Li Boyang Zheng Boyang Zheng Junhai Wang Shunyan Chen Yang Wang Fei Ge Beibei Qin Beibei Qin Xiaoqing Zheng Xiaoqing Zheng Yuqing Deng Yuqing Deng Ruihong Zeng Ruihong Zeng |
| author_facet | Hanglin Li Linyan Ma Wenjian Li Wenjian Li Boyang Zheng Boyang Zheng Junhai Wang Shunyan Chen Yang Wang Fei Ge Beibei Qin Beibei Qin Xiaoqing Zheng Xiaoqing Zheng Yuqing Deng Yuqing Deng Ruihong Zeng Ruihong Zeng |
| author_sort | Hanglin Li |
| collection | DOAJ |
| description | BackgroundInfants with respiratory syncytial virus (RSV)-associated bronchiolitis are at increased risk of childhood asthma. Recent studies demonstrated that certain infections induce innate immune memory (also termed trained immunity), especially in macrophages, to respond more strongly to future stimuli with broad specificity, involving in human inflammatory diseases. Metabolic reprogramming increases the capacity of the innate immune cells to respond to a secondary stimulation, is a crucial step for the induction of trained immunity. We hypothesize that specific metabolic reprogramming of lung trained macrophages induced by neonatal respiratory infection is crucial for childhood allergic asthma.ObjectiveTo address the role of metabolic reprogramming in lung trained macrophages induced by respiratory virus infection in allergic asthma.MethodsNeonatal mice were infected and sensitized by the natural rodent pathogen Pneumonia virus of mice (PVM), a mouse equivalent strain of human RSV, combined with ovalbumin (OVA). Lung CD11b+ macrophages in the memory phase were re-stimulated to investigate trained immunity and metabonomics. Adoptive transfer, metabolic inhibitor and restore experiments were used to explore the role of specific metabolic reprogramming in childhood allergic asthma.ResultsPVM infection combined with OVA sensitization in neonatal mice resulted in non-Th2 (Th1/Th17) type allergic asthma following OVA challenge in childhood of mice. Lung CD11b+ macrophages in the memory phage increased, and showed enhanced inflammatory responses following re-stimulation, suggesting trained macrophages. Adoptive transfer of the trained macrophages mediated the allergic asthma in childhood. The trained macrophages showed metabolic reprogramming after re-stimulation. Notably, proline biosynthesis remarkably increased. Inhibition of proline biosynthesis suppressed the development of the trained macrophages as well as the Th1/Th17 type allergic asthma, while supplement of proline recovered the trained macrophages as well as the allergic asthma.ConclusionProline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to development of allergic asthma in childhood. Proline metabolism could be a well target for prevention of allergic asthma in childhood. |
| first_indexed | 2024-04-11T20:05:14Z |
| format | Article |
| id | doaj.art-de3112a03a4842c8affbece889c5c3c6 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T20:05:14Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-de3112a03a4842c8affbece889c5c3c62022-12-22T04:05:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.977235977235Proline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to development of allergic asthma in childhood of miceHanglin Li0Linyan Ma1Wenjian Li2Wenjian Li3Boyang Zheng4Boyang Zheng5Junhai Wang6Shunyan Chen7Yang Wang8Fei Ge9Beibei Qin10Beibei Qin11Xiaoqing Zheng12Xiaoqing Zheng13Yuqing Deng14Yuqing Deng15Ruihong Zeng16Ruihong Zeng17Department of Immunology, Hebei Medical University, Shijiazhuang, ChinaDepartment of Immunology, Hebei Medical University, Shijiazhuang, ChinaDepartment of Immunology, Hebei Medical University, Shijiazhuang, ChinaKey Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Hebei Medical University, Shijiazhuang, ChinaDepartment of Immunology, Hebei Medical University, Shijiazhuang, ChinaThe Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Immunology, Hebei Medical University, Shijiazhuang, ChinaDepartment of Immunology, Hebei Medical University, Shijiazhuang, ChinaDepartment of Immunology, Hebei Medical University, Shijiazhuang, ChinaDepartment of Immunology, Hebei Medical University, Shijiazhuang, ChinaDepartment of Immunology, Hebei Medical University, Shijiazhuang, ChinaClinical Lab, Hebei Provincial People’s Hospital, Shijiazhuang, ChinaDepartment of Immunology, Hebei Medical University, Shijiazhuang, ChinaKey Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Hebei Medical University, Shijiazhuang, ChinaDepartment of Immunology, Hebei Medical University, Shijiazhuang, ChinaKey Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Hebei Medical University, Shijiazhuang, ChinaDepartment of Immunology, Hebei Medical University, Shijiazhuang, ChinaKey Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Hebei Medical University, Shijiazhuang, ChinaBackgroundInfants with respiratory syncytial virus (RSV)-associated bronchiolitis are at increased risk of childhood asthma. Recent studies demonstrated that certain infections induce innate immune memory (also termed trained immunity), especially in macrophages, to respond more strongly to future stimuli with broad specificity, involving in human inflammatory diseases. Metabolic reprogramming increases the capacity of the innate immune cells to respond to a secondary stimulation, is a crucial step for the induction of trained immunity. We hypothesize that specific metabolic reprogramming of lung trained macrophages induced by neonatal respiratory infection is crucial for childhood allergic asthma.ObjectiveTo address the role of metabolic reprogramming in lung trained macrophages induced by respiratory virus infection in allergic asthma.MethodsNeonatal mice were infected and sensitized by the natural rodent pathogen Pneumonia virus of mice (PVM), a mouse equivalent strain of human RSV, combined with ovalbumin (OVA). Lung CD11b+ macrophages in the memory phase were re-stimulated to investigate trained immunity and metabonomics. Adoptive transfer, metabolic inhibitor and restore experiments were used to explore the role of specific metabolic reprogramming in childhood allergic asthma.ResultsPVM infection combined with OVA sensitization in neonatal mice resulted in non-Th2 (Th1/Th17) type allergic asthma following OVA challenge in childhood of mice. Lung CD11b+ macrophages in the memory phage increased, and showed enhanced inflammatory responses following re-stimulation, suggesting trained macrophages. Adoptive transfer of the trained macrophages mediated the allergic asthma in childhood. The trained macrophages showed metabolic reprogramming after re-stimulation. Notably, proline biosynthesis remarkably increased. Inhibition of proline biosynthesis suppressed the development of the trained macrophages as well as the Th1/Th17 type allergic asthma, while supplement of proline recovered the trained macrophages as well as the allergic asthma.ConclusionProline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to development of allergic asthma in childhood. Proline metabolism could be a well target for prevention of allergic asthma in childhood.https://www.frontiersin.org/articles/10.3389/fimmu.2022.977235/fullallergic asthmatrained macrophagesinnate immune memoryproline metabolism reprogrammingrespiratory virus infection |
| spellingShingle | Hanglin Li Linyan Ma Wenjian Li Wenjian Li Boyang Zheng Boyang Zheng Junhai Wang Shunyan Chen Yang Wang Fei Ge Beibei Qin Beibei Qin Xiaoqing Zheng Xiaoqing Zheng Yuqing Deng Yuqing Deng Ruihong Zeng Ruihong Zeng Proline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to development of allergic asthma in childhood of mice Frontiers in Immunology allergic asthma trained macrophages innate immune memory proline metabolism reprogramming respiratory virus infection |
| title | Proline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to development of allergic asthma in childhood of mice |
| title_full | Proline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to development of allergic asthma in childhood of mice |
| title_fullStr | Proline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to development of allergic asthma in childhood of mice |
| title_full_unstemmed | Proline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to development of allergic asthma in childhood of mice |
| title_short | Proline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to development of allergic asthma in childhood of mice |
| title_sort | proline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to development of allergic asthma in childhood of mice |
| topic | allergic asthma trained macrophages innate immune memory proline metabolism reprogramming respiratory virus infection |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.977235/full |
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