How Does Hiv Affect The Human Immune System – The natural course of human immunodeficiency virus type 1 (HIV-1) infection is characterized by high viral load, immune cell exhaustion, and immunodeficiency, which ultimately leads to the stage of acquired immunodeficiency syndrome (AIDS) and opportunistic infections. People who develop HIV-1 rapidly die from AIDS years later without treatment. The introduction of ART has significantly extended the life expectancy of people living with HIV. However, because HIV-infected cells remain latent in some patients, immune function is incompletely reconstructed after ART. Therefore, how to achieve a functional cure is always a focus and hot spot in global AIDS research. Fortunately, the emergence of ECs/LTNPs, which can naturally control viral replication, has given rise to new hope for a functional AIDS cure. Recently, attention has been paid to a special category of infected individuals who are more likely to develop the disease than the natural progression of HIV-1 infection described above. These patients are characterized by years of HIV-1 infection, long-term asymptomatic status, and normal CD4+T cell counts without ART, classified as HIV-infected long-term progressors (LTNPs) and elite controllers (ECs). Numerous studies have shown that the host and the virus together determine the progression of HIV-1 infection, with the level of innate immune activation playing an important role. As the first line of defense against pathogenic invasion, innate immunity is also a bridge to adaptive immunity. Compared with natural progression, innate immunity plays an antiviral role in HIV-1 infection by inducing or activating many innate immune factors in natural ECs. Learning the regulation of EC immunity, especially the innate immunity of various characteristics, and thus studying the mechanism of natural control of the disease development will contribute to the realization of a functional cure of AIDS. Therefore, this review explores the relationship between innate immunity and disease progression in the ECS of HIV-1 infection from the aspects of innate immune cells, signaling pathways, and cytokines, which may help provide new targets and theoretical references for functional treatment, prevention. . and AIDS control and vaccine development.
HIV, the human immunodeficiency virus, can cause the gradual loss of immune function and eventually lead to acquired immunodeficiency syndrome (AIDS). AIDS is a major public health problem worldwide, posing a serious threat to human health and social stability. There is currently no effective vaccine or drug. HIV can be divided into HIV-1 and HIV-2. The global distribution of the HIV-1 epidemic and the global distribution of the different strains vary greatly (1, 2). According to the World Health Organization, by the end of 2020, 37,700,000 people will be living with HIV worldwide, 1,500,000 people will become newly infected with HIV in 2020, and 680,000 patients will die from HIV-related causes. 1 Infection is a dynamic process at different rates. disease progression. People who develop HIV-1 rapidly die from AIDS years later without treatment. The introduction of ART has significantly increased life expectancy and reduced mortality among people infected with HIV (3). However, HIV-infected patients are unable to eradicate the virus even with lifelong ART because of latent viral reservoir (LVR) (4). Therefore, the researchers proposed the concept of a functional cure for AIDS, which refers to long-term control of HIV replication after stopping treatment to maintain normal CD4+ T-cell count and function. Even if patients carry the virus, their viral load is below the detection limit and they do not have typical pathological symptoms. However, how to achieve a functional AIDS cure is always the focus and hot spot of global AIDS research. So far, functional cure has been achieved in EC/CTNPs, who still have replicating viruses and low levels of latent reservoir, but the body can spontaneously and efficiently control the virus below detection limits without ART. Compared with the natural progression of HIV infection, HIV-1-infected natural elite controllers are a special group of HIV-infected patients, including LTNP and EC, who bring new hope and a turning point for a functional cure. LTNPs refer to patients who have been infected with HIV-1 for 10 years or more but have never received antiretroviral therapy (ART) and maintain normal CD4+ T-lymphocyte counts (>500/μL). In these patients, the immune system maintains a long-term stable state (5). LNTPs account for approximately 5% of all individuals infected with HIV-1 (6); LTNPs with a viral load < 50 copies/ml are called EC, which accounts for approximately 0.1 – 1%.
How Does Hiv Affect The Human Immune System
Numerous studies have shown that host and virus together determine disease progression after HIV-1 infection, with the level of innate immune activation playing an important role ( 7 , 8 ). Currently, much is known about the adaptive immune mechanism of natural controllers of HIV-1 infection, but relatively little is known about the role of innate immunity. As the first line of defense against invading pathogens, innate immunity is also a bridge to induced adaptive immunity. Pattern recognition receptors recognize HIV infection, and a series of immune cell responses are then recruited to activate or deactivate innate immune factors to play an antiviral role ( 9 ). These innate immune components (10) include a number of soluble factors such as skin mucosal epithelial cells, phagocytes, NK cells, as well as cytokines, chemokines, and small molecules such as complement and mannose-binding lectin. Together, these elements form a rapid response system against infection and play a role in preventing the spread of infection. In addition, antigen-presenting cells such as dendritic cells and monocytes play specific roles in innate and adaptive immunity. Therefore, further understanding of the mechanisms and effects of HIV innate immunity will help provide new targets and theoretical insights for the functional cure, prevention and control of AIDS and the development of vaccines. This review discusses the mechanisms observed in the natural progression of HIV infection, the role of LTNPs and ECs in innate immune cells, pattern recognition receptors, signaling pathways, soluble factors, and then the relationship between innate immunity and disease progression after HIV infection. . reference for further studies on HIV infection in natural ECs.
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Innate immune cells play an important role in the initiation of HIV infection and remain active until the final events that characterize AIDS, including monocytes/macrophages, dendritic cells, NK cells, NKT cells, γδ T cells, B1 cells, mast cells, and various granulocytes. (11). Among these cells, DCs, NK cells, macrophage cells, and NKT cells play important and indispensable roles in innate immunity in the population of HIV-infected ECs/LTNPs, while other innate immune cells are less effective or understudied. be As potent antigen-presenting cells, dendritic cells play a critical role in the host’s early response to viruses. They can not only modulate the rapid host response to pathogens but also stimulate adaptive immunity (12). With regard to NK cells, there is substantial evidence that NK cells play a key role in the control of chronic HIV infection through antibody-mediated cytotoxicity or secretion of soluble cytokines. NK cell activation is mediated in part by pro-inflammatory cytokines secreted by dendritic cells and monocytes, including IL-15 and IFN-α. In addition, macrophages are the main effector cells involved in the late innate immune response. They actively cooperate by recruiting inflammatory cells by secreting many cytokines, such as IL-1 and TNF-α ( 13 ), and have an important effect on immune responses to the virus. NKT cells involve complex interactions between different immune cells and have a strong immunomodulatory effect. Currently, many studies have shown that these innate immune cells are very important to affect the course of the disease after HIV LTNPs / ECs invade the human body. So, in this section, we mainly discuss the cellular immune function of these innate immune cells, ECs or LTNPs, and we briefly discuss or discuss other innate immune cells. The association of some key innate immune cells after HIV infection in EC/LTNPs is illustrated in Figure 1 .
Figure 1 Communication of some key innate immune cells after HIV infection of ECs/LTNPs. ① ECs/LTNPs, DCs are activated, the number of cells increases, and cytokines such as IFN-α and IL-12 are released to play the role of antiviral infection. At the same time, these cytokines can activate macrophages and NKT cells. ② When macrophages are activated in EC/LTNPs, the number of macrophages increases and they have strong phagocytosis for infected cells. At the same time, secretion of inflammatory cytokines such as IFN-α, IFN-β, TNF-α, and IL-12 increases, which control viral replication and activate NK cells. ③ When NK cells are activated by ECs/LTNPs, the number of cells increases and can directly kill infected cells. At the same time, its cellular activity increases and releases IFN-γ, TNF-α, which further activates macrophages and induces monocytes to transform into DCs. ④ Upon activation of NKT cells and ECs/LTNPs, the secretion of IL-2, IFN-γ, and other cytokines increases, which further activate DCs and NK cells. HIV-infected ECs or LTNPs, these immune cells together play a role in antiviral infection.
Dendritic cells are the most potent type of antigen-presenting cells (APCs) and play a crucial role in the entire process of HIV infection. according to
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