HIV-Related Immune Activation and Inflammation: Current Understanding and Strategies

Cao, Wei; Li, Taisheng

doi:10.1155/2021/7316456

Cited by 93 publications

(66 citation statements)

References 136 publications

(155 reference statements)

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“…Despite advancements in antiretroviral therapy, the frequency of inflammation and immune activation remains elevated in patients with HIV infection, and these conditions are associated with morbidity and mortality [ 124 , 125 ]. The role of the gut microbiota in persistent HIV infection of the intestinal immune system is an interesting topic.…”

Section: Hivmentioning

confidence: 99%

Role of Microbiota in Viral Infections and Pathological Progression

Mizutani

Ishizaka

Koga

et al. 2022

Viruses

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Viral infections are influenced by various microorganisms in the environment surrounding the target tissue, and the correlation between the type and balance of commensal microbiota is the key to establishment of the infection and pathogenicity. Some commensal microorganisms are known to resist or promote viral infection, while others are involved in pathogenicity. It is also becoming evident that the profile of the commensal microbiota under normal conditions influences the progression of viral diseases. Thus, to understand the pathogenesis underlying viral infections, it is important to elucidate the interactions among viruses, target tissues, and the surrounding environment, including the commensal microbiota, which should have different relationships with each virus. In this review, we outline the role of microorganisms in viral infections. Particularly, we focus on gaining an in-depth understanding of the correlations among viral infections, target tissues, and the surrounding environment, including the commensal microbiota and the gut virome, and discussing the impact of changes in the microbiota (dysbiosis) on the pathological progression of viral infections.

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Section: Hivmentioning

confidence: 99%

Role of Microbiota in Viral Infections and Pathological Progression

Mizutani

Ishizaka

Koga

et al. 2022

Viruses

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“…Persistent immune activation played a prominent role in the loss of CD4 + T cells and disease progression during HIV infection ( 6 , 7 ). High levels of immune activation occurred early in primary HIV infection and still existed in PLWH who were receiving effective ART ( 8 , 9 ). Indeed, immune activation is a key factor that leads to impaired immune reconstitution ( 10 , 11 ).…”

Section: Introductionmentioning

confidence: 99%

Decreased CD73+ Double-Negative T Cells and Elevated Level of Soluble CD73 Correlated With and Predicted Poor Immune Reconstitution in HIV-Infected Patients After Antiretroviral Therapy

Wang

Zhang

et al. 2022

Front. Immunol.

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Although extensive use of antiretroviral therapy (ART) has made great progress in controlling HIV replication and improving CD4+ T cell recovery, the immune reconstitution remained insufficient in some patients, who were defined as poor immunological responders (PIRs). These PIRs were at a high risk of AIDS-related and non-AIDS complications, resulting in higher morbidity and mortality rate. Thus, it is a major challenge and urgently needed to distinguish PIRs early and improve their immune function in time. Immune activation is a key factor that leads to impaired immune reconstitution in people living with HIV (PLWH) who are receiving effective ART. Double negative T cells (DNT) were reported to associate with the control of immune activation during HIV infection. However, the precise mechanisms by which DNT cells exerted their suppressive capacity during HIV infection remained puzzled. CD73, both a soluble and a membrane-bound form, display immunosuppressive effects through producing adenosine (ADO). Thus, whether DNT cells expressed CD73 and mediated immune suppression through CD73-ADO pathway needs to be investigated. Here, we found a significant downregulation of CD73 expression on DNT cells in treatment-naïve PLWH (TNs) compared to healthy controls, accompanied with increased concentration of sCD73 in plasma. Both the frequency of CD73+ DNT cells and the level of plasma sCD73 recovered after ART treatment. However, PIRs showed decreased percentage of CD73+ DNT cells compared to immunological responders (IRs). The frequency of CD73+ DNT cells was positively correlated with CD4+ T cell count and CD4/CD8 ratio, and negatively correlated with immune activation in PLWH. The level of sCD73 also showed a negative correlation to CD4+ T cell count and CD4/CD8 ratio. More importantly, in the present cohort, a higher level of sCD73 at the time of initiating ART could predict poor immune reconstitution in PLWH after long-term ART. Our findings highlighted the importance of CD73+ DNT cells and sCD73 in the disease progression and immune reconstitution of PLWH, and provided evidences for sCD73 as a potential biomarker of predicting immune recovery.

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“…This is consistent with an idea that time-limited exposure to the viral components induces not only a specific adaptive immune response, but also stimulates a much broader training of innate immune cells. The effect of chronic viral infection on innate immunity is unknown, but persistent inflammation associated with chronic HCV (21) or HIV (22) infection is consistent with an enhancing training rather than tolerance, and can be explained by an enhanced response of trained innate immune cells to TLR stimulation. Increased inflammatory responses may underlie pathogenesis of HIV-associated co-morbidities, making characterization of trained immunity during HIV infection a priority.…”

Section: Mechanisms Of Trained Immunitymentioning

confidence: 99%

Trained Immunity and HIV Infection

2022

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Findings that certain infections induce immunity not only against the causing agent, but also against an unrelated pathogen have intrigued investigators for many years. Recently, underlying mechanisms of this phenomenon have started to come to light. It was found that the key cells responsible for heterologous protection are innate immune cells such as natural killer cells (NKs), dendritic cells, and monocytes/macrophages. These cells are ‘primed’ by initial infection, allowing them to provide enhanced response to subsequent infection by the same or unrelated agent. This phenomenon of innate immune memory was termed ‘trained immunity’. The proposed mechanism for trained immunity involves activation by the first stimulus of metabolic pathways that lead to epigenetic changes, which maintain the cell in a “trained” state, allowing enhanced responses to a subsequent stimulus. Innate immune memory can lead either to enhanced responses or to suppression of subsequent responses (‘tolerance’), depending on the strength and length of the initial stimulation of the immune cells. In the context of HIV infection, innate memory induced by infection is not well understood. In this Hypothesis and Theory article, we discuss evidence for HIV-induced trained immunity in human monocytes, its possible mechanisms, and implications for HIV-associated co-morbidities.

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HIV-Related Immune Activation and Inflammation: Current Understanding and Strategies

Cited by 93 publications

References 136 publications

Role of Microbiota in Viral Infections and Pathological Progression

Role of Microbiota in Viral Infections and Pathological Progression

Decreased CD73+ Double-Negative T Cells and Elevated Level of Soluble CD73 Correlated With and Predicted Poor Immune Reconstitution in HIV-Infected Patients After Antiretroviral Therapy

Trained Immunity and HIV Infection

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