HIV infection and aging of the innate immune system

The increased life expectancy of HIV-infected individuals due to improved treatment has revealed an unexpected increase in non-AIDS comorbidities that are typically associated with older age including cardiovascular disease, dementia and frailty. The majority of these diseases arise as the result of dysregulated systemic inflammation, and both the aged and HIV-infected individuals exhibit elevated basal levels of inflammation. In the elderly, increased inflammation and age-related diseases are associated with a state of impaired immunity called immunosenescence, which is thought to result from a lifetime of immune stimulation. It is now apparent that HIV induces premature immunosenescence within T-cells; however, the impact of HIV on aging of cells of the innate arm of the immune system is unknown. Innate immune cells play a central role in inflammation and are thus critical for the pathogenesis of inflammatory diseases. Limited evidence suggests HIV infection mimics age-related changes to innate immune cells; however, the extent of this effect and the mechanism underlying these changes remain to be defined. This review focuses on the impact of HIV infection on the function and aging of innate immune cells and discusses potential drivers of premature immunosenescence including chronic endotoxaemia, residual viraemia, telomere attrition and altered cellular signalling.

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Immune cells—A curse and a blessing!

Journal of Experimental Medicine ◽

10.1084/jem.20210590 ◽

2021 ◽

Vol 218 (6) ◽

Author(s):

Valbona Mirakaj

Keyword(s):

Cardiovascular Disease ◽

Immune System ◽

Immune Cells ◽

Innate Immune System ◽

Innate Immune ◽

Innate Immune Cells ◽

The Impact

Innate immune cells are crucial in the development and regulation of cardiovascular disease. In this issue, two groups, Davis et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20201839) and Li et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20210008) describe the impact of the innate immune system on the development of cardiovascular disease.

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Overcoming immune dysfunction in the elderly: trained immunity as a novel approach

International Immunology ◽

10.1093/intimm/dxaa052 ◽

2020 ◽

Vol 32 (12) ◽

pp. 741-753 ◽

Cited By ~ 1

Author(s):

Ozlem Bulut ◽

Gizem Kilic ◽

Jorge Domínguez-Andrés ◽

Mihai G Netea

Keyword(s):

Immune System ◽

Immune Cells ◽

The Elderly ◽

Innate Immune ◽

Metabolic Reprogramming ◽

Advanced Age ◽

Innate Immune Cells ◽

Trained Immunity ◽

Adaptive Immune Cells ◽

Novel Approach

Abstract People with advanced age have a higher susceptibility to infections and exhibit increased mortality and morbidity as the ability of the immune system to combat infections decreases with age. While innate immune cells display functional defects such as decreased phagocytosis, chemotaxis and cytokine production, adaptive immune cells exhibit reduced receptor diversity, defective antibody production and a sharp decline in naive cell populations. Successful responses to vaccination in the elderly are critical to prevent common infections such as influenza and pneumonia, but vaccine efficacy decreases in older individuals compared with young adults. Trained immunity is a newly emerging concept that showed that innate immune cells possess non-specific immunological memory established through epigenetic and metabolic reprogramming upon encountering certain pathogenic stimuli. Clinical studies suggest that trained immunity can be utilized to enhance immune responses against infections and improve the efficiency of vaccinations in adults; however, how trained immunity responses are shaped with advanced age is still an open question. In this review, we provide an overview of the age-related changes in the immune system with a focus on innate immunity, discuss current vaccination strategies for the elderly, present the concept of trained immunity and propose it as a novel approach to enhance responses against infections and vaccinations in the elderly population.

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Why Target Innate Immune Cells in Cancers?

Cancers ◽

10.3390/cancers13040690 ◽

2021 ◽

Vol 13 (4) ◽

pp. 690

Author(s):

Mary Poupot

Keyword(s):

Immune System ◽

Cancer Cells ◽

Immune Cells ◽

Innate Immune ◽

Innate Immune Cells

The immune system is a smart way to fight cancer, with its precise targeting of cancer cells sparing healthy cells [...]

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Adipocytes, Innate Immunity and Obesity: A Mini-Review

Frontiers in Immunology ◽

10.3389/fimmu.2021.650768 ◽

2021 ◽

Vol 12 ◽

Author(s):

Alecia M. Blaszczak ◽

Anahita Jalilvand ◽

Willa A. Hsueh

Keyword(s):

Adipose Tissue ◽

Immune System ◽

Immune Cells ◽

Adaptive Immune System ◽

Innate Immune ◽

Lymphoid Cells ◽

Innate Immune Cells ◽

Adaptive Immune

The role of adipose tissue (AT) inflammation in obesity and its multiple related-complications is a rapidly expanding area of scientific interest. Within the last 30 years, the role of the adipocyte as an endocrine and immunologic cell has been progressively established. Like the macrophage, the adipocyte is capable of linking the innate and adaptive immune system through the secretion of adipokines and cytokines; exosome release of lipids, hormones, and microRNAs; and contact interaction with other immune cells. Key innate immune cells in AT include adipocytes, macrophages, neutrophils, and innate lymphoid cells type 2 (ILC2s). The role of the innate immune system in promoting adipose tissue inflammation in obesity will be highlighted in this review. T cells and B cells also play important roles in contributing to AT inflammation and are discussed in this series in the chapter on adaptive immunity.

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HIV infection: focus on the innate immune cells

Immunologic Research ◽

10.1007/s12026-016-8862-2 ◽

2016 ◽

Vol 64 (5-6) ◽

pp. 1118-1132 ◽

Cited By ~ 14

Author(s):

Milena S. Espíndola ◽

Luana S. Soares ◽

Leonardo J. Galvão-Lima ◽

Fabiana A. Zambuzi ◽

Maira C. Cacemiro ◽

...

Keyword(s):

Hiv Infection ◽

Immune Cells ◽

Innate Immune ◽

Innate Immune Cells ◽

Infection Focus

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TLR agonists enhance responsiveness of inflammatory innate immune cells in HLA-B*57-positive HIV patients

Journal of Molecular Medicine ◽

10.1007/s00109-020-01996-7 ◽

2020 ◽

Vol 99 (1) ◽

pp. 147-158

Author(s):

L. Dold ◽

L. Zimmer ◽

C. Schwarze-Zander ◽

C. Boesecke ◽

R. Mohr ◽

...

Keyword(s):

Hiv Infection ◽

Nk Cells ◽

Immune Cells ◽

Nk Cell ◽

Innate Immune ◽

Innate Immune Cells ◽

Double Positive ◽

Hiv Patients ◽

Ifn Gamma ◽

Tlr Agonists

Abstract HLA-B*57 affects the course of HIV infection. Under antiretroviral therapy, its effects cannot be explained by outstandingly efficient T cell responses alone but may also involve cells of innate immunity. Studying in vitro stimulation with Pam3CSK4, E. coli LPS-B5 and CpG-ODN-2216, we observed greater induction of IL-6/IL-1beta double-positive CD14+CD16++ monocytes as well as IFN-gamma-positive cytotoxic CD56highCD16neg NK cells in HLA-B*57- versus HLA-B*44-positive HIV patients, while TNF-alpha induction remained unchanged. Differences were not seen in the other monocyte and NK cell subsets or in HLA-matched healthy controls. Our findings show that, in virally suppressed HIV infection, HLA-B*57 is associated with enhanced responsiveness of inflammatory innate immune cells to TLR ligands, possibly contributing to increased vulnerability in sepsis. Key messages • HLA-B*57 is a host factor affecting clinical outcomes of HIV infection. • HLA-B*57 modifies inflammatory subsets of NK cells and monocytes in HIV infection. • In HLA-B*57-positive HIV patients TLR agonists induce enhanced IL-6/IL-1beta in monocytes. • NK cells from HLA-B*57 HIV patients release more IFN-gamma upon TLR costimulation. • HLA-B*57 is linked to enhanced inflammatory responsiveness to TLR ligands.

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Evidence for B cell maturation but not trained immunity in uninfected infants exposed to hepatitis C virus

Gut ◽

10.1136/gutjnl-2019-320269 ◽

2020 ◽

Vol 69 (12) ◽

pp. 2203-2213 ◽

Cited By ~ 1

Author(s):

Anton Lutckii ◽

Benedikt Strunz ◽

Anton Zhirkov ◽

Olga Filipovich ◽

Elena Rukoiatkina ◽

...

Keyword(s):

Immune System ◽

B Cells ◽

B Cell ◽

Immune Cells ◽

Immune Cell ◽

Innate Immune ◽

Cell Maturation ◽

Innate Immune Cells ◽

B Cell Maturation ◽

Exposed Uninfected

ObjectivesVertical transmission of hepatitis C virus (HCV) is rare compared with other chronic viral infections, despite that newborns have an immature, and possibly more susceptible, immune system. It further remains unclear to what extent prenatal and perinatal exposure to HCV affects immune system development in neonates.DesignTo address this, we studied B cells, innate immune cells and soluble factors in a cohort of 62 children that were either unexposed, exposed uninfected or infected with HCV. Forty of these infants were followed longitudinally from birth up until 18 months of age.ResultsAs expected, evidence for B cell maturation was observed with increased age in children, whereas few age-related changes were noticed among innate immune cells. HCV-infected children had a high frequency of HCV-specific IgG-secreting B cells. Such a response was also detected in some exposed but uninfected children but not in uninfected controls. Consistent with this, both HCV-exposed uninfected and HCV-infected infants had evidence of early B cell immune maturation with an increased proportion of IgA-positive plasma cells and upregulated CD40 expression. In contrast, actual HCV viraemia, but not mere exposure, led to alterations within myeloid immune cell populations, natural killer (NK) cells and a distinct soluble factor profile with increased levels of inflammatory cytokines and chemokines.ConclusionOur data reveal that exposure to, and infection with, HCV causes disparate effects on adaptive B cells and innate immune cell such as myeloid cells and NK cells in infants.

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A Novel Regulatory Player in the Innate Immune System: Long Non-Coding RNAs

International Journal of Molecular Sciences ◽

10.3390/ijms22179535 ◽

2021 ◽

Vol 22 (17) ◽

pp. 9535

Author(s):

Yuhuai Xie ◽

Yuanyuan Wei

Keyword(s):

Immune System ◽

Immune Cells ◽

Innate Immune System ◽

Molecular Mechanisms ◽

Innate Immune ◽

Innate Immune Cells ◽

Immune Mediated ◽

Development And Differentiation ◽

Non Coding Rnas ◽

And Function

Long non-coding RNAs (lncRNAs) represent crucial transcriptional and post-transcriptional gene regulators during antimicrobial responses in the host innate immune system. Studies have shown that lncRNAs are expressed in a highly tissue- and cell-specific- manner and are involved in the differentiation and function of innate immune cells, as well as inflammatory and antiviral processes, through versatile molecular mechanisms. These lncRNAs function via the interactions with DNA, RNA, or protein in either cis or trans pattern, relying on their specific sequences or their transcriptions and processing. The dysregulation of lncRNA function is associated with various human non-infectious diseases, such as inflammatory bowel disease, cardiovascular diseases, and diabetes mellitus. Here, we provide an overview of the regulation and mechanisms of lncRNA function in the development and differentiation of innate immune cells, and during the activation or repression of innate immune responses. These elucidations might be beneficial for the development of therapeutic strategies targeting inflammatory and innate immune-mediated diseases.

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Therapies Targeting Trained Immune Cells in Inflammatory and Autoimmune Diseases

Frontiers in Immunology ◽

10.3389/fimmu.2020.631743 ◽

2021 ◽

Vol 11 ◽

Author(s):

Cristina Municio ◽

Gabriel Criado

Keyword(s):

Autoimmune Diseases ◽

Immune Cells ◽

Inflammatory Diseases ◽

Cell Metabolism ◽

Innate Immune ◽

Epigenetic Reprogramming ◽

Innate Immune Cells ◽

Tissue Destruction ◽

Specific Stimulus ◽

Trained Immunity

The concept of trained immunity has recently emerged as a mechanism contributing to several immune mediated inflammatory conditions. Trained immunity is defined by the immunological memory developed in innate immune cells after a primary non-specific stimulus that, in turn, promotes a heightened inflammatory response upon a secondary challenge. The most characteristic changes associated to this process involve the rewiring of cell metabolism and epigenetic reprogramming. Under physiological conditions, the role of trained immune cells ensures a prompt response. This action is limited by effective resolution of inflammation and tissue repair in order to restore homeostasis. However, unrestrained activation of innate immune cells contributes to the development of chronic inflammation and tissue destruction through the secretion of inflammatory cytokines, proteases and growth factors. Therefore, interventions aimed at reversing the changes induced by trained immunity provide potential therapeutic approaches to treat inflammatory and autoimmune diseases like rheumatoid arthritis (RA). We review cellular approaches that target metabolism and the epigenetic reprogramming of dendritic cells, macrophages, natural killer cells, and other trained cells in the context of autoimmune inflammatory diseases.

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