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The new research provides a new perspective to clarify the reduction mechanism of CD4+ T cells in AIDS patients and provides a new perspective for the development of drugs targeting NLRP3 inflammasome and pyrolysis The theoretical basis.
(Screenshot of website article) On March 15, 2021, the team of Academician Wang Fusheng from the Fifth Medical Center of PLA General Hospital published a titled "NLRP3 inflammasome induces CD4+ T-cell loss in chronically HIV-1-infected in the Journal of Clinical Investigation, an internationally renowned medical journal.
The research results of "NLRP3 inflammasome induces the reduction of CD4+ T cells in chronic HIV-1 infected patients), for the first time clarified that the pyrolysis in AIDS patients and the sustained inflammatory response caused by it is the progressive decrease of CD4+ T lymphocytes And the key reasons for disease progression provide a scientific basis for optimizing clinical programs and improving the effectiveness of clinical treatment.
The main target cells of human immunodeficiency virus (HIV) infecting the human body are CD4+ T cells.
Due to the continuous replication and destruction of the virus, the number of CD4+ T cells in the infected person's body gradually decreases, the patient's immunity is severely exhausted, and various opportunistic infections occur.
The risk is increased, but the key mechanism of CD4+ T cell destruction is not fully understood.
Apoptosis and pyroptosis are the two main forms of cell death.
Apoptosis depends on the activation of Caspase-3, which is a kind of "quiet" death.
Pyrolysis is a kind of cell lysis that relies on inflammasomes (inflammasome) to activate inflammatory caspases after sensing pathogens or danger signals, and to induce cell lysis by cutting Gasdermin protein.
It has a strong ability to induce inflammation [1].Previously, there was still no clear answer to the death method of CD4+ T lymphocytes in AIDS patients.
In response to the above problems, the research team analyzed the death mode of CD4+ T cells in the peripheral blood and lymph node tissues of AIDS patients, and found for the first time that as the HIV disease progresses, the proportion of CD4+ T cell apoptosis and pyrolysis has gradually increased, and it is related to HIV infection.
The degree of inflammation in the body is positively correlated.
Especially in the lymph nodes, the researchers found that the CD4+ T cells that undergo pyrolysis are mainly located in the lymphoid follicles and are closely related to the level of HIV replication in the patient.
For example, HIV-positive signals and apoptotic CD4+ T cells (active-Caspase-3 positive) are mainly located in the lymphoid follicular area (see Figure 1).
This work confirmed for the first time the mechanism of CD4+ T reduction in AIDS patients: CD4+ T cells actively replicating HIV virus are prone to apoptosis; bystander CD4+ T cells that are not infected by the virus are prone to pyrolysis due to inflammation [2-3].
Figure 1: HIV-positive signals and apoptotic CD4 T cells (active-Caspase-3 positive) are mainly located in the lymphatic follicle area.
Further studies have found that the activation of NLRP3 inflammasomes mediated by reactive oxygen species is involved in HIV-induced CD4+ T The cell scorches.
Chronic HIV infection leads to significant up-regulation of NLRP3 inflammasome-related signals in patients’ cells, which are in a state of high pyroptosis-inducing potential.
In untreated patients, HIV virus particles can induce reactive oxygen species (ROS) activation and induce inflammasomes like receptor family 3 (NLRP3) by co-receptor with CD4+ T cell surface (signal 1), independent of the establishment of infection.
Mediated capsase-1 activation and pyrolysis; in patients with viral suppression, continuous inflammation (signal 2) or TCR homologous antigen stimulation (signal 3) can still induce cell pyrolysis through this pathway (see Figure 2 ).
This suggests that NLRP3 is a potential intervention target for the control of CD4+ T cell pyrolysis in HIV-infected patients.
Figure 2: Persistent inflammation (signal 2) or TCR homologous antigen stimulation (signal 3) can still induce pyrolysis through this pathway.
In summary, this study provides the elucidation of the reduction mechanism of CD4+ T cells in AIDS patients This new perspective provides a theoretical basis for the development of drugs targeting NLRP3 inflammasome and pyrolysis in the treatment of AIDS.
Dr.
Chao Zhang, Dr.
Song Jinwen, Dr.
Huang Huihuang, and Dr.
Fan Xing from the Department of Infectious Disease Medicine, Fifth Medical Center of PLA General Hospital are the co-first authors of this article, and Academician Wang Fusheng is the corresponding author.
The research was completed under the funding of the Innovation Group Project of the National Natural Science Foundation of China, which also received strong support from Academician Shao Feng of the Beijing Institute of Biological Sciences.
References[1] Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, et al.
Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.
Cell Death Differ.
2018;25( 3):486.
[2] Doitsh G, Cavrois M, Lassen KG, Zepeda O, Yang Z, Santiago ML, et al.
Abortive HIV infection mediates CD4 T cell depletion and inflammation in human lymphoid tissue.
Cell.
2010;143( 5):789-801.
[3] Doitsh G, Galloway NL, Geng X, Yang Z, Monroe KM, Zepeda O, et al.
Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection.
Nature.
2014 ; 505(7484):509.
Introduction of experts Academician Wang Fusheng, Academician of Chinese Academy of Sciences, Chief Physician.
Director of the Department of Infectious Disease Medicine of the Fifth Medical Center of the PLA General Hospital; Director of the National Clinical Research Center for Infectious Diseases; Experts of the National Novel Coronavirus Joint Prevention and Control Working Mechanism Scientific Research Expert Group; Experts of the 8th Disciplinary Appraisal Group of the Academic Degrees Committee of the State Council, National and Expert of the Military Biosafety Expert Group; winner of the National Award for Innovation, National Outstanding Scientific and Technological Worker, National Advanced Individual in Fighting the New Coronary Pneumonia Epidemic, National Outstanding Communist Party Member, Military Science and Technology Leader, National Outstanding Youth Fund Winner, Chinese Medical Association Infection Director-designate of the Branch of Diseases.
Disclaimer: This content is only for Chinese medical and health professionals, and aims to provide and only provide scientific information to medical and health professionals for personal learning and reference purposes.
If you are not a medical and health professional, please do not participate or spread it.
The new research provides a new perspective to clarify the reduction mechanism of CD4+ T cells in AIDS patients and provides a new perspective for the development of drugs targeting NLRP3 inflammasome and pyrolysis The theoretical basis.
(Screenshot of website article) On March 15, 2021, the team of Academician Wang Fusheng from the Fifth Medical Center of PLA General Hospital published a titled "NLRP3 inflammasome induces CD4+ T-cell loss in chronically HIV-1-infected in the Journal of Clinical Investigation, an internationally renowned medical journal.
The research results of "NLRP3 inflammasome induces the reduction of CD4+ T cells in chronic HIV-1 infected patients), for the first time clarified that the pyrolysis in AIDS patients and the sustained inflammatory response caused by it is the progressive decrease of CD4+ T lymphocytes And the key reasons for disease progression provide a scientific basis for optimizing clinical programs and improving the effectiveness of clinical treatment.
The main target cells of human immunodeficiency virus (HIV) infecting the human body are CD4+ T cells.
Due to the continuous replication and destruction of the virus, the number of CD4+ T cells in the infected person's body gradually decreases, the patient's immunity is severely exhausted, and various opportunistic infections occur.
The risk is increased, but the key mechanism of CD4+ T cell destruction is not fully understood.
Apoptosis and pyroptosis are the two main forms of cell death.
Apoptosis depends on the activation of Caspase-3, which is a kind of "quiet" death.
Pyrolysis is a kind of cell lysis that relies on inflammasomes (inflammasome) to activate inflammatory caspases after sensing pathogens or danger signals, and to induce cell lysis by cutting Gasdermin protein.
It has a strong ability to induce inflammation [1].Previously, there was still no clear answer to the death method of CD4+ T lymphocytes in AIDS patients.
In response to the above problems, the research team analyzed the death mode of CD4+ T cells in the peripheral blood and lymph node tissues of AIDS patients, and found for the first time that as the HIV disease progresses, the proportion of CD4+ T cell apoptosis and pyrolysis has gradually increased, and it is related to HIV infection.
The degree of inflammation in the body is positively correlated.
Especially in the lymph nodes, the researchers found that the CD4+ T cells that undergo pyrolysis are mainly located in the lymphoid follicles and are closely related to the level of HIV replication in the patient.
For example, HIV-positive signals and apoptotic CD4+ T cells (active-Caspase-3 positive) are mainly located in the lymphoid follicular area (see Figure 1).
This work confirmed for the first time the mechanism of CD4+ T reduction in AIDS patients: CD4+ T cells actively replicating HIV virus are prone to apoptosis; bystander CD4+ T cells that are not infected by the virus are prone to pyrolysis due to inflammation [2-3].
Figure 1: HIV-positive signals and apoptotic CD4 T cells (active-Caspase-3 positive) are mainly located in the lymphatic follicle area.
Further studies have found that the activation of NLRP3 inflammasomes mediated by reactive oxygen species is involved in HIV-induced CD4+ T The cell scorches.
Chronic HIV infection leads to significant up-regulation of NLRP3 inflammasome-related signals in patients’ cells, which are in a state of high pyroptosis-inducing potential.
In untreated patients, HIV virus particles can induce reactive oxygen species (ROS) activation and induce inflammasomes like receptor family 3 (NLRP3) by co-receptor with CD4+ T cell surface (signal 1), independent of the establishment of infection.
Mediated capsase-1 activation and pyrolysis; in patients with viral suppression, continuous inflammation (signal 2) or TCR homologous antigen stimulation (signal 3) can still induce cell pyrolysis through this pathway (see Figure 2 ).
This suggests that NLRP3 is a potential intervention target for the control of CD4+ T cell pyrolysis in HIV-infected patients.
Figure 2: Persistent inflammation (signal 2) or TCR homologous antigen stimulation (signal 3) can still induce pyrolysis through this pathway.
In summary, this study provides the elucidation of the reduction mechanism of CD4+ T cells in AIDS patients This new perspective provides a theoretical basis for the development of drugs targeting NLRP3 inflammasome and pyrolysis in the treatment of AIDS.
Dr.
Chao Zhang, Dr.
Song Jinwen, Dr.
Huang Huihuang, and Dr.
Fan Xing from the Department of Infectious Disease Medicine, Fifth Medical Center of PLA General Hospital are the co-first authors of this article, and Academician Wang Fusheng is the corresponding author.
The research was completed under the funding of the Innovation Group Project of the National Natural Science Foundation of China, which also received strong support from Academician Shao Feng of the Beijing Institute of Biological Sciences.
References[1] Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, et al.
Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.
Cell Death Differ.
2018;25( 3):486.
[2] Doitsh G, Cavrois M, Lassen KG, Zepeda O, Yang Z, Santiago ML, et al.
Abortive HIV infection mediates CD4 T cell depletion and inflammation in human lymphoid tissue.
Cell.
2010;143( 5):789-801.
[3] Doitsh G, Galloway NL, Geng X, Yang Z, Monroe KM, Zepeda O, et al.
Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection.
Nature.
2014 ; 505(7484):509.
Introduction of experts Academician Wang Fusheng, Academician of Chinese Academy of Sciences, Chief Physician.
Director of the Department of Infectious Disease Medicine of the Fifth Medical Center of the PLA General Hospital; Director of the National Clinical Research Center for Infectious Diseases; Experts of the National Novel Coronavirus Joint Prevention and Control Working Mechanism Scientific Research Expert Group; Experts of the 8th Disciplinary Appraisal Group of the Academic Degrees Committee of the State Council, National and Expert of the Military Biosafety Expert Group; winner of the National Award for Innovation, National Outstanding Scientific and Technological Worker, National Advanced Individual in Fighting the New Coronary Pneumonia Epidemic, National Outstanding Communist Party Member, Military Science and Technology Leader, National Outstanding Youth Fund Winner, Chinese Medical Association Infection Director-designate of the Branch of Diseases.
Disclaimer: This content is only for Chinese medical and health professionals, and aims to provide and only provide scientific information to medical and health professionals for personal learning and reference purposes.
If you are not a medical and health professional, please do not participate or spread it.
