The TLR7/IRF-5 axis sensitizes memory CD4+ T cells to Fas-mediated apoptosis during HIV-1 infection.

HIV-1 infection is characterized by inflammation and a progressive decline in CD4+ T cell count. Despite treatment with antiretroviral therapy (ART), the majority of people living with HIV (PLWH) maintain residual levels of inflammation, a low degree of immune activation, and higher sensitivity to cell death in their memory CD4+ T cell compartment. To date, the mechanisms responsible for this high sensitivity remain elusive.

Autophagy-dependent glutaminolysis drives superior IL21 production in HIV-1-specific CD4 T cells.

The maintenance of a strong IL21 production in memory CD4 T cells, especially in HIV-1-specific cells, represents a major correlate of natural immune protection against the virus. However, the molecular mechanisms underlying IL21 production during HIV-1 infection, which is only elevated among the naturally protected elite controllers (EC), are still unknown. We recently found out that lipophagy is a critical immune mediator that control an antiviral metabolic state following CD8A T cell receptor engagement, playing an important role in the natural control of HIV-1 infection.

Latest developments in tryptophan metabolism: Understanding its role in B cell immunity.

One of the most essential and important building blocks of life is the tryptophan amino acid. As such, the pathways surrounding its metabolism are often crucial for the maintenance of proper cell activity and homeostasis. The ratios of tryptophan to kynurenine, mainly mediated by indoleamine 2,3-dioxygenase activity, is a key parameter in the inflammation as well as immunomodulation of both aseptic and septic diseases.

Lipophagy confers a key metabolic advantage that ensures protective CD8A T-cell responses against HIV-1.

Although macroautophagy/autophagy has been proposed as a critical defense mechanism against HIV-1 by targeting viral components for degradation, its contribution as a catabolic process in providing optimal anti-HIV-1 immunity has never been addressed. The failure to restore proper antiviral CD8A/CD8 T-cell immunity, especially against HIV-1, is still the major limitation of current antiretroviral therapies. Consequently, it is of clinical imperative to provide new strategies to enhance the function of HIV-1-specific CD8A T-cells in patients under antiretroviral treatments (ART).

Cannabinoid-Induced Immunomodulation during Viral Infections: A Focus on Mitochondria.

This review examines the impact of cannabinoids on viral infections, as well as its effects on the mitochondria of the nervous and immune system. The paper conveys information about the beneficial and negative impacts of cannabinoids on viral infections, especially HIV-1. These include effects on the inflammatory response as well as neuroprotective effects.

Plasticity in T-cell mitochondrial metabolism: A necessary peacekeeper during the troubled times of persistent HIV-1 infection.

The notion of immuno-metabolism refers to the crosstalk between key metabolic pathways and the development/maintenance of protective immunity in the context of physiological processes and anti-microbial defenses. Enthusiasm for immuno-metabolism in the context of HIV-1 infection, especially among T-cell lineages, continues to grow over time as science opens new therapeutic perspectives to limit viral pathogenesis and to boost anti-viral responses. The idea of "metabolism as a therapeutic target" is called metabolic reprogramming and is based on the use of specific metabolism-targeting drugs that are currently available for cancer therapy.

USP18 is a significant driver of memory CD4 T-cell reduced viability caused by type I IFN signaling during primary HIV-1 infection.

The loss of Memory CD4 T-cells (Mem) is a major hallmark of HIV-1 immuno-pathogenesis and occurs early during the first months of primary infection. A lot of effort has been put into understanding the molecular mechanisms behind this loss, yet they still have not been fully identified. In this study, we unveil the unreported role of USP18 in the deleterious effects of sustained type I IFN signaling on Mem, including HIV-1-specific CD4 T-cells.

IRF-5 Promotes Cell Death in CD4 T Cells during Chronic Infection.

The transcription factor interferon regulatory factor 5 (IRF-5) plays an important function in innate immunity and in initiating pro-inflammatory responses against pathogens. IRF-5 is constitutively expressed in several cell types, including plasmacytoid dendritic cells, monocytes, and B cells. We have previously reported that IRF-5 is also expressed in T cells during infection.

Deciphering natural control of HIV-1: A valuable strategy to achieve antiretroviral therapy termination.

Antiretroviral therapy (ART) has dramatically reduced HIV-1-associated morbidity and mortality, and has transformed HIV-1 infection into a manageable chronic condition by suppressing viral replication. However, despite recent patient care improvements, ART still fails to cure HIV-1 infection due to the inability to counteract immune defects and metabolic disturbances that are associated with residual inflammation alongside viral persistence. Life-long drug administration also results in multiple side-effects in patients including lipodystrophy and insulin resistance.

Sustained IFN-I Expression during Established Persistent Viral Infection: A "Bad Seed" for Protective Immunity.

Type I interferons (IFN-I) are one of the primary immune defenses against viruses. Similar to all other molecular mechanisms that are central to eliciting protective immune responses, IFN-I expression is subject to homeostatic controls that regulate cytokine levels upon clearing the infection. However, in the case of established persistent viral infection, sustained elevation of IFN-I expression bears deleterious effects to the host and is today considered as the major driver of inflammation and immunosuppression.

Kynurenine Reduces Memory CD4 T-Cell Survival by Interfering with Interleukin-2 Signaling Early during HIV-1 Infection.

Unlabelled: Early HIV-1 infection is characterized by enhanced tryptophan catabolism, which contributes to immune suppression and disease progression. However, the mechanism by which kynurenine, a tryptophan-related metabolite, induces immune suppression remains poorly understood. Herein, we show that the increased production of kynurenine correlates with defective interleukin-2 (IL-2) signaling in memory CD4 T cells from HIV-infected subjects.