Immune Dysfunctions of CD56neg NK Cells Are Associated With HIV-1 Disease Progression
BackgroundPopulations of natural killer cells lacking CD56 expression [CD56neg natural killer (NK) cells] have been demonstrated to expand during human immunodeficiency virus (HIV)-1 infection. However, their phenotypic and functional characteristics have not been systematically analyzed, and their...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.811091/full |
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| author | Wen-Jing Cao Xiao-Chang Zhang Lin-Yu Wan Lin-Yu Wan Qing-Yu Li Xiu-Ying Mu An-Liang Guo Ming-Ju Zhou Li-Li Shen Li-Li Shen Chao Zhang Xing Fan Yan-Mei Jiao Ruo-Nan Xu Chun-Bao Zhou Jin-Hong Yuan Sheng-Qi Wang Fu-Sheng Wang Fu-Sheng Wang Jin-Wen Song |
| author_facet | Wen-Jing Cao Xiao-Chang Zhang Lin-Yu Wan Lin-Yu Wan Qing-Yu Li Xiu-Ying Mu An-Liang Guo Ming-Ju Zhou Li-Li Shen Li-Li Shen Chao Zhang Xing Fan Yan-Mei Jiao Ruo-Nan Xu Chun-Bao Zhou Jin-Hong Yuan Sheng-Qi Wang Fu-Sheng Wang Fu-Sheng Wang Jin-Wen Song |
| author_sort | Wen-Jing Cao |
| collection | DOAJ |
| description | BackgroundPopulations of natural killer cells lacking CD56 expression [CD56neg natural killer (NK) cells] have been demonstrated to expand during human immunodeficiency virus (HIV)-1 infection. However, their phenotypic and functional characteristics have not been systematically analyzed, and their roles during disease progression remain poorly understood.MethodsIn this study, 84 donors, namely 34 treatment-naïve HIV-1-infected patients (TNs), 29 HIV-1-infected patients with successful antiretroviral therapy (ARTs), and 21 healthy controls (HCs), were enrolled. The phenotypic and functional characteristics of CD56neg NK cells were analyzed using single-cell RNA-sequencing (scRNA-seq) and flow cytometry. A potential link between the characteristics of CD56neg NK cells and the clinical parameters associated with HIV-1 disease progression was examined.ResultsThe frequency of the CD56neg NK cell population was significantly increased in TNs, which could be partially rescued by ART. Flow cytometry analyses revealed that CD56neg NK cells were characterized by high expression of CD39, TIGIT, CD95, and Ki67 compared to CD56dim NK cells. In vitro assays revealed reduced IFN-γ and TNF-α secretion, as well as decreased expression of granzyme B and perforin in CD56neg NK cells. In line with the data obtained by flow cytometry, scRNA-seq analysis further demonstrated impaired cytotoxic activities of CD56neg NK cells. Notably, a negative correlation was observed between CD39, CD95, and Ki67 expression levels in CD56neg NK cells and CD4+ T cell counts.ConclusionsThe results presented in this study indicate that the CD56neg NK cell population expanded in HIV-1-infected individuals is dysfunctional and closely correlates with HIV-1 disease progression. |
| first_indexed | 2024-04-11T20:57:30Z |
| format | Article |
| id | doaj.art-953c6ebbd5a44ec1bb714f798b455ce9 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T20:57:30Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-953c6ebbd5a44ec1bb714f798b455ce92022-12-22T04:03:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-01-011210.3389/fimmu.2021.811091811091Immune Dysfunctions of CD56neg NK Cells Are Associated With HIV-1 Disease ProgressionWen-Jing Cao0Xiao-Chang Zhang1Lin-Yu Wan2Lin-Yu Wan3Qing-Yu Li4Xiu-Ying Mu5An-Liang Guo6Ming-Ju Zhou7Li-Li Shen8Li-Li Shen9Chao Zhang10Xing Fan11Yan-Mei Jiao12Ruo-Nan Xu13Chun-Bao Zhou14Jin-Hong Yuan15Sheng-Qi Wang16Fu-Sheng Wang17Fu-Sheng Wang18Jin-Wen Song19The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaBeijing Institute of Radiation Medicine, Beijing, ChinaDepartment of Clinical Medicine, Bengbu Medical College, Bengbu, ChinaDepartment of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, ChinaBeijing Institute of Radiation Medicine, Beijing, ChinaDepartment of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, ChinaDepartment of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, ChinaDepartment of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, ChinaDepartment of Clinical Medicine, Bengbu Medical College, Bengbu, ChinaDepartment of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, ChinaDepartment of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, ChinaDepartment of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, ChinaDepartment of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, ChinaDepartment of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, ChinaDepartment of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, ChinaDepartment of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, ChinaBeijing Institute of Radiation Medicine, Beijing, ChinaThe First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaDepartment of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, ChinaDepartment of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, ChinaBackgroundPopulations of natural killer cells lacking CD56 expression [CD56neg natural killer (NK) cells] have been demonstrated to expand during human immunodeficiency virus (HIV)-1 infection. However, their phenotypic and functional characteristics have not been systematically analyzed, and their roles during disease progression remain poorly understood.MethodsIn this study, 84 donors, namely 34 treatment-naïve HIV-1-infected patients (TNs), 29 HIV-1-infected patients with successful antiretroviral therapy (ARTs), and 21 healthy controls (HCs), were enrolled. The phenotypic and functional characteristics of CD56neg NK cells were analyzed using single-cell RNA-sequencing (scRNA-seq) and flow cytometry. A potential link between the characteristics of CD56neg NK cells and the clinical parameters associated with HIV-1 disease progression was examined.ResultsThe frequency of the CD56neg NK cell population was significantly increased in TNs, which could be partially rescued by ART. Flow cytometry analyses revealed that CD56neg NK cells were characterized by high expression of CD39, TIGIT, CD95, and Ki67 compared to CD56dim NK cells. In vitro assays revealed reduced IFN-γ and TNF-α secretion, as well as decreased expression of granzyme B and perforin in CD56neg NK cells. In line with the data obtained by flow cytometry, scRNA-seq analysis further demonstrated impaired cytotoxic activities of CD56neg NK cells. Notably, a negative correlation was observed between CD39, CD95, and Ki67 expression levels in CD56neg NK cells and CD4+ T cell counts.ConclusionsThe results presented in this study indicate that the CD56neg NK cell population expanded in HIV-1-infected individuals is dysfunctional and closely correlates with HIV-1 disease progression.https://www.frontiersin.org/articles/10.3389/fimmu.2021.811091/fullHIV-1CD56neg NK cellsscRNA-seqCD39dysfunction |
| spellingShingle | Wen-Jing Cao Xiao-Chang Zhang Lin-Yu Wan Lin-Yu Wan Qing-Yu Li Xiu-Ying Mu An-Liang Guo Ming-Ju Zhou Li-Li Shen Li-Li Shen Chao Zhang Xing Fan Yan-Mei Jiao Ruo-Nan Xu Chun-Bao Zhou Jin-Hong Yuan Sheng-Qi Wang Fu-Sheng Wang Fu-Sheng Wang Jin-Wen Song Immune Dysfunctions of CD56neg NK Cells Are Associated With HIV-1 Disease Progression Frontiers in Immunology HIV-1 CD56neg NK cells scRNA-seq CD39 dysfunction |
| title | Immune Dysfunctions of CD56neg NK Cells Are Associated With HIV-1 Disease Progression |
| title_full | Immune Dysfunctions of CD56neg NK Cells Are Associated With HIV-1 Disease Progression |
| title_fullStr | Immune Dysfunctions of CD56neg NK Cells Are Associated With HIV-1 Disease Progression |
| title_full_unstemmed | Immune Dysfunctions of CD56neg NK Cells Are Associated With HIV-1 Disease Progression |
| title_short | Immune Dysfunctions of CD56neg NK Cells Are Associated With HIV-1 Disease Progression |
| title_sort | immune dysfunctions of cd56neg nk cells are associated with hiv 1 disease progression |
| topic | HIV-1 CD56neg NK cells scRNA-seq CD39 dysfunction |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.811091/full |
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