Single-cell atlas of murine adrenal glands reveals immune-adrenal crosstalk during systemic Candida albicans infection
Fungal sepsis remains a major health threat with high mortality, where the adrenal gland stress response has been rarely reported. Candida albicans (C.albicans) is the most common opportunistic fungal pathogen of life-threatening disseminated candidiasis and fungal sepsis. In the present study, we p...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.966814/full |
| _version_ | 1811255971688742912 |
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| author | Kai Zhang Kai Zhang Kai Zhang Kai Zhang Yuzhe Hu Yuzhe Hu Yuzhe Hu Ruoyu Li Ruoyu Li Ruoyu Li Ruoyu Li Ting Li Ting Li Ting Li |
| author_facet | Kai Zhang Kai Zhang Kai Zhang Kai Zhang Yuzhe Hu Yuzhe Hu Yuzhe Hu Ruoyu Li Ruoyu Li Ruoyu Li Ruoyu Li Ting Li Ting Li Ting Li |
| author_sort | Kai Zhang |
| collection | DOAJ |
| description | Fungal sepsis remains a major health threat with high mortality, where the adrenal gland stress response has been rarely reported. Candida albicans (C.albicans) is the most common opportunistic fungal pathogen of life-threatening disseminated candidiasis and fungal sepsis. In the present study, we performed single-cell RNA sequencing (scRNA-Seq) using the 10x Genomics platform to analyze the changes in murine adrenal transcriptome following systemic C.albicans infection. A total of 16 021 cells were categorized into 18 transcriptionally distinct clusters, representing adrenocortical cells, endothelial cells, various immune cells, mesenchymal cells, smooth muscle cells, adrenal capsule, chromaffin cells, neurons and glials. As the main cell component in the adrenal gland responsible for steroidogenesis, the adrenocortical cells dramatically diminished and were further grouped into 10 subclusters, which differently distributed in the infected and uninfected samples. Pseudo-time analysis revealed transitions of the adrenocortical cells from the initial normal states to active or dysfunctional states following systemic C.albicans infection via two trajectory paths. Endothelial cells in the highly vascularized organ of adrenal gland further proliferated following infection, with the upregulation of genes positively regulating angiogenesis and downregulation of protective genes of endothelial cells. Immune cells were also excessively infiltrated in adrenal glands of C.albicans-infected mice. Macrophages dominated the immune microenvironments in murine adrenal glands both before and after C.albicans infection, mediating the crosstalk among the steroid-producing cells, endothelial cells and immune cells within the adrenal gland. NLR family, pyrin domain containing 3 (NLRP3, encoded by Nlrp3) and complement receptor 3 (CR3, encoded by Itgam) were found to be significantly upregulated on the adrenal macrophages upon systemic C.albicans infection and might play critical roles in mediating the myeloid response. Meanwhile, the number and strength of the interactions between the infiltrating immune cells and adrenal resident cells were unveiled by cell-cell communication analysis to be dramatically increased after systemic C.albicans infection, indicating that the immune-adrenal crosstalk might contribute to the compromised functions of adrenal cells. Overall, our comprehensive picture of the murine adrenal gland microenvironment in systemic C.albicans infection provides deeper insights into the immune-adrenal cell communications during fungal sepsis. |
| first_indexed | 2024-04-12T17:32:36Z |
| format | Article |
| id | doaj.art-113b19bdd3d64f01a366d9ef7a115180 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T17:32:36Z |
| publishDate | 2022-11-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-113b19bdd3d64f01a366d9ef7a1151802022-12-22T03:23:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.966814966814Single-cell atlas of murine adrenal glands reveals immune-adrenal crosstalk during systemic Candida albicans infectionKai Zhang0Kai Zhang1Kai Zhang2Kai Zhang3Yuzhe Hu4Yuzhe Hu5Yuzhe Hu6Ruoyu Li7Ruoyu Li8Ruoyu Li9Ruoyu Li10Ting Li11Ting Li12Ting Li13Department of Dermatology and Venerology, Peking University First Hospital, Beijing, ChinaNational Clinical Research Center for Skin and Immune Diseases, Beijing, ChinaResearch Center for Medical Mycology, Peking University, Beijing, ChinaBeijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, ChinaDepartment of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Medical Immunology, National Health Commission of the People's Republic of China, Beijing, ChinaPeking University Center for Human Disease Genomics, Beijing, ChinaDepartment of Dermatology and Venerology, Peking University First Hospital, Beijing, ChinaNational Clinical Research Center for Skin and Immune Diseases, Beijing, ChinaResearch Center for Medical Mycology, Peking University, Beijing, ChinaBeijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, ChinaDepartment of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Medical Immunology, National Health Commission of the People's Republic of China, Beijing, ChinaPeking University Center for Human Disease Genomics, Beijing, ChinaFungal sepsis remains a major health threat with high mortality, where the adrenal gland stress response has been rarely reported. Candida albicans (C.albicans) is the most common opportunistic fungal pathogen of life-threatening disseminated candidiasis and fungal sepsis. In the present study, we performed single-cell RNA sequencing (scRNA-Seq) using the 10x Genomics platform to analyze the changes in murine adrenal transcriptome following systemic C.albicans infection. A total of 16 021 cells were categorized into 18 transcriptionally distinct clusters, representing adrenocortical cells, endothelial cells, various immune cells, mesenchymal cells, smooth muscle cells, adrenal capsule, chromaffin cells, neurons and glials. As the main cell component in the adrenal gland responsible for steroidogenesis, the adrenocortical cells dramatically diminished and were further grouped into 10 subclusters, which differently distributed in the infected and uninfected samples. Pseudo-time analysis revealed transitions of the adrenocortical cells from the initial normal states to active or dysfunctional states following systemic C.albicans infection via two trajectory paths. Endothelial cells in the highly vascularized organ of adrenal gland further proliferated following infection, with the upregulation of genes positively regulating angiogenesis and downregulation of protective genes of endothelial cells. Immune cells were also excessively infiltrated in adrenal glands of C.albicans-infected mice. Macrophages dominated the immune microenvironments in murine adrenal glands both before and after C.albicans infection, mediating the crosstalk among the steroid-producing cells, endothelial cells and immune cells within the adrenal gland. NLR family, pyrin domain containing 3 (NLRP3, encoded by Nlrp3) and complement receptor 3 (CR3, encoded by Itgam) were found to be significantly upregulated on the adrenal macrophages upon systemic C.albicans infection and might play critical roles in mediating the myeloid response. Meanwhile, the number and strength of the interactions between the infiltrating immune cells and adrenal resident cells were unveiled by cell-cell communication analysis to be dramatically increased after systemic C.albicans infection, indicating that the immune-adrenal crosstalk might contribute to the compromised functions of adrenal cells. Overall, our comprehensive picture of the murine adrenal gland microenvironment in systemic C.albicans infection provides deeper insights into the immune-adrenal cell communications during fungal sepsis.https://www.frontiersin.org/articles/10.3389/fimmu.2022.966814/fullfungal sepsissystemic Candida albicans infectionadrenal glandsingle-cell RNA sequencingimmune-adrenal crosstalk |
| spellingShingle | Kai Zhang Kai Zhang Kai Zhang Kai Zhang Yuzhe Hu Yuzhe Hu Yuzhe Hu Ruoyu Li Ruoyu Li Ruoyu Li Ruoyu Li Ting Li Ting Li Ting Li Single-cell atlas of murine adrenal glands reveals immune-adrenal crosstalk during systemic Candida albicans infection Frontiers in Immunology fungal sepsis systemic Candida albicans infection adrenal gland single-cell RNA sequencing immune-adrenal crosstalk |
| title | Single-cell atlas of murine adrenal glands reveals immune-adrenal crosstalk during systemic Candida albicans infection |
| title_full | Single-cell atlas of murine adrenal glands reveals immune-adrenal crosstalk during systemic Candida albicans infection |
| title_fullStr | Single-cell atlas of murine adrenal glands reveals immune-adrenal crosstalk during systemic Candida albicans infection |
| title_full_unstemmed | Single-cell atlas of murine adrenal glands reveals immune-adrenal crosstalk during systemic Candida albicans infection |
| title_short | Single-cell atlas of murine adrenal glands reveals immune-adrenal crosstalk during systemic Candida albicans infection |
| title_sort | single cell atlas of murine adrenal glands reveals immune adrenal crosstalk during systemic candida albicans infection |
| topic | fungal sepsis systemic Candida albicans infection adrenal gland single-cell RNA sequencing immune-adrenal crosstalk |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.966814/full |
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