Mitochondrial disturbance related to increased caspase-1 of CD4+T cells in HIV-1 infection
Abstract Background In HIV-1 infection, more than 95% of CD4+T cells die of caspase-1 mediated pyroptosis. What governs the increased susceptibility of CD4+T cells to pyroptosis is poorly understood. Methods Blood samples were obtained from 31 untreated HIV-infected patients (UNT), 29 antiretroviral...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | BMC Infectious Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12879-023-08485-5 |
| _version_ | 1797276687991308288 |
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| author | Fengting Yu Chengjie Ma Xia Jin Hongxin Zhao Jiang Xiao Li Li Shujing Song Xiaohui Xie Siyuan Yang Yunxia Tang Linghang Wang Fujie Zhang |
| author_facet | Fengting Yu Chengjie Ma Xia Jin Hongxin Zhao Jiang Xiao Li Li Shujing Song Xiaohui Xie Siyuan Yang Yunxia Tang Linghang Wang Fujie Zhang |
| author_sort | Fengting Yu |
| collection | DOAJ |
| description | Abstract Background In HIV-1 infection, more than 95% of CD4+T cells die of caspase-1 mediated pyroptosis. What governs the increased susceptibility of CD4+T cells to pyroptosis is poorly understood. Methods Blood samples were obtained from 31 untreated HIV-infected patients (UNT), 29 antiretroviral therapy treated HIV-infected patients (ART), and 21 healthy control donors (HD). Plasma levels of IL-18 and IL-1β, caspase-1 expression, mitochondrial mass (MM) and mitochondrial fusion/fisson genes of CD4+T subsets were measured. Results A significantly higher IL-18 level in plasma and MM level of CD4+T cells were found in HIV-infected patients (UNT and ART) compared to HD, and the MMhigh phenotype was manifested, related to increased caspase-1 expression. Moreover, the increased MM was more pronounced in the early differentiated and inactivated CD4+T cells. However, higher MM was not intrinsically linked to T cell differentiation disorder or excessive activation of the CD4+T cells. Mechanistically, the increased MM was significantly correlated with an elevated level of expression of the mitochondrial fusion gene mitofusin1. Conclusion An increase in MM was associated with heightened sensitivity of CD4+T cells to pyroptosis, even in early differentiated and inactivated CD4+T cells, in patients with HIV-1 infection, regardless of whether patients were on antiretroviral therapy or not. These new revelations have uncovered a previously unappreciated challenge to immune reconstitution with antiretroviral therapy. |
| first_indexed | 2024-03-07T15:32:42Z |
| format | Article |
| id | doaj.art-843a175bc30447119a064199664f1cea |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-03-07T15:32:42Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj.art-843a175bc30447119a064199664f1cea2024-03-05T16:21:09ZengBMCBMC Infectious Diseases1471-23342024-01-0124111110.1186/s12879-023-08485-5Mitochondrial disturbance related to increased caspase-1 of CD4+T cells in HIV-1 infectionFengting Yu0Chengjie Ma1Xia Jin2Hongxin Zhao3Jiang Xiao4Li Li5Shujing Song6Xiaohui Xie7Siyuan Yang8Yunxia Tang9Linghang Wang10Fujie Zhang11Medical School, University of Chinese Academy of SciencesBeijing Ditan Hospital, Capital Medical UniversityHuman Viral Diseases and Vaccine Translation Research Unit, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of SciencesBeijing Ditan Hospital, Capital Medical UniversityBeijing Ditan Hospital, Capital Medical UniversityBeijing Ditan Hospital, Capital Medical UniversityBeijing Ditan Hospital, Capital Medical UniversityDepartment of Infectious Diseases, Peking University Ditan Teaching, HospitalBeijing Ditan Hospital, Capital Medical UniversityBeijing Ditan Hospital, Capital Medical UniversityBeijing Ditan Hospital, Capital Medical UniversityMedical School, University of Chinese Academy of SciencesAbstract Background In HIV-1 infection, more than 95% of CD4+T cells die of caspase-1 mediated pyroptosis. What governs the increased susceptibility of CD4+T cells to pyroptosis is poorly understood. Methods Blood samples were obtained from 31 untreated HIV-infected patients (UNT), 29 antiretroviral therapy treated HIV-infected patients (ART), and 21 healthy control donors (HD). Plasma levels of IL-18 and IL-1β, caspase-1 expression, mitochondrial mass (MM) and mitochondrial fusion/fisson genes of CD4+T subsets were measured. Results A significantly higher IL-18 level in plasma and MM level of CD4+T cells were found in HIV-infected patients (UNT and ART) compared to HD, and the MMhigh phenotype was manifested, related to increased caspase-1 expression. Moreover, the increased MM was more pronounced in the early differentiated and inactivated CD4+T cells. However, higher MM was not intrinsically linked to T cell differentiation disorder or excessive activation of the CD4+T cells. Mechanistically, the increased MM was significantly correlated with an elevated level of expression of the mitochondrial fusion gene mitofusin1. Conclusion An increase in MM was associated with heightened sensitivity of CD4+T cells to pyroptosis, even in early differentiated and inactivated CD4+T cells, in patients with HIV-1 infection, regardless of whether patients were on antiretroviral therapy or not. These new revelations have uncovered a previously unappreciated challenge to immune reconstitution with antiretroviral therapy.https://doi.org/10.1186/s12879-023-08485-5HIV/AIDSCD4+T pyroptosisMitochondrial massMFN1 |
| spellingShingle | Fengting Yu Chengjie Ma Xia Jin Hongxin Zhao Jiang Xiao Li Li Shujing Song Xiaohui Xie Siyuan Yang Yunxia Tang Linghang Wang Fujie Zhang Mitochondrial disturbance related to increased caspase-1 of CD4+T cells in HIV-1 infection BMC Infectious Diseases HIV/AIDS CD4+T pyroptosis Mitochondrial mass MFN1 |
| title | Mitochondrial disturbance related to increased caspase-1 of CD4+T cells in HIV-1 infection |
| title_full | Mitochondrial disturbance related to increased caspase-1 of CD4+T cells in HIV-1 infection |
| title_fullStr | Mitochondrial disturbance related to increased caspase-1 of CD4+T cells in HIV-1 infection |
| title_full_unstemmed | Mitochondrial disturbance related to increased caspase-1 of CD4+T cells in HIV-1 infection |
| title_short | Mitochondrial disturbance related to increased caspase-1 of CD4+T cells in HIV-1 infection |
| title_sort | mitochondrial disturbance related to increased caspase 1 of cd4 t cells in hiv 1 infection |
| topic | HIV/AIDS CD4+T pyroptosis Mitochondrial mass MFN1 |
| url | https://doi.org/10.1186/s12879-023-08485-5 |
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