Trained immunity: A “new” weapon in the fight against infectious diseases

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: March 13, 2023

Innate immune cells can potentiate the response to reinfection through an innate form of immunological memory known as trained immunity. The potential this fast-acting, nonspecific compared traditional adaptive in prophylaxis and therapy has been a topic great interest many fields, including infectious diseases. Amidst rise antimicrobial resistance climate change—two major threats global health—, harnessing advantages immunity forms could be game-changing. Here, we present recent works bridging disease that raise important discoveries, questions, concerns, novel avenues for modulation practice. By exploring progress bacterial, viral, fungal, parasitic diseases, equally highlight future directions with focus on particularly problematic and/or understudied pathogens.

Language: Английский

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Weight cycling induces innate immune memory in adipose tissue macrophages

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 11, 2023

Introduction Weight loss improves obesity-associated diabetes risk. However, most individuals regain weight, which worsens the risk of developing and cardiovascular disease. We previously reported that male mice retain immunological changes even after weight loss, suggesting immune cells may remember state obesity. Therefore, we hypothesized cycles gain otherwise known as cycling, can induce innate memory in adipose macrophages. Methods Bone marrow derived macrophages were primed with palmitic acid or tissue conditioned media a culture model memory. Mice also put on low fat high diets over 14-27 weeks to gain, cycling. Results Priming from obese increased maximal glycolysis oxidative phosphorylation LPS-induced TNFα IL-6 production. Palmitic effects dependent TLR4 impaired by methyltransferase inhibition AMPK activation. While improved glucose tolerance mice, for greater activation subsequent stimulation LPS ex vivo measured cytokine In had elevated metabolism secreted higher levels basal TNFα, prime heighted regain. Discussion Together, these data suggest following obesity enhanced inflammation upon This response contribute worsened

Language: Английский

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Damage-mediated macrophage polarization in sterile inflammation

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 3, 2023

Most of the leading causes death, such as cardiovascular diseases, cancer, dementia, neurodegenerative and many more, are associated with sterile inflammation, either a cause or consequence these conditions. The ability to control progression inflammation toward tissue resolution before it becomes chronic holds significant clinical potential. During initiation occurs through damage-associated molecular patterns (DAMPs) in absence pathogen-associated molecules. Macrophages, which primarily localized tissue, play pivotal role sensing DAMPs. Furthermore, macrophages can also detect respond resolution-associated (RAMPs) specific pro-resolving mediators (SPMs) during inflammation. being highly adaptable cells, particularly influenced by changes microenvironment. In response environment, monocytes, pro-inflammatory macrophages, pro-resolution modulate their differentiation state. Ultimately, DAMP RAMP-primed depending on predominant subpopulation, regulate balance between inflammatory resolving processes. While injury pathogen-induced reactions may have distinct effects most studies focused macrophage responses induced pathogens. this review, emphasizes available human data, we illustrate how sense examining expression receptors for DAMPs, RAMPs, SPMs. We delve into signaling pathways SPMs, contribute regulation from phenotype. Understanding regulatory mechanisms behind transition subtypes offer insights manipulating diseases.

Language: Английский

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Hematopoietic Stem Cells and the Immune System in Development and Aging

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5862 - 5862

Published: March 20, 2023

Hematopoietic stem cells (HSCs) support haematopoiesis throughout life and give rise to the whole variety of immune system. Developing in early embryo, passing through precursor stage, maturing into first HSCs, they undergo a fairly large number divisions while maintaining high regenerative potential due repair activity. This is greatly reduced adult HSCs. They go state dormancy anaerobic metabolism maintain their stemness life. However, with age, changes occur pool HSCs that negatively affect effectiveness immunity. Niche aging accumulation mutations age reduces ability self-renew differentiation potential. accompanied by decrease clonal diversity disturbance lymphopoiesis (decrease formation naive T- B-cells) predominance myeloid haematopoiesis. Aging also affects mature cells, regardless HSC, therefore, phagocytic activity intensity oxidative burst decrease, efficiency processing presentation antigens impaired. innate adaptive immunity produce factors form chronic inflammatory background. All these processes have serious negative impact on protective properties system, increasing inflammation, risk developing autoimmune, oncological, cardiovascular diseases age. Understanding mechanisms reducing comparative analysis embryonic features will allow us get closer deciphering programs for development, aging, regeneration rejuvenation

Language: Английский

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The causes and consequences of trained immunity in myeloid cells

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 11, 2024

Conventionally, immunity in humans has been classified as innate and adaptive, with the concept that only latter type an immunological memory/recall response against specific antigens or pathogens. Recently, a new of trained (a.k.a. memory response) emerged. According to this concept, immune cells can exhibit enhanced responsiveness subsequent challenges, after initial stimulation antigen/pathogen. Thus, enables respond robustly non-specifically through exposure re-exposure antigens/infections vaccines, providing resistance unrelated pathogens reduced infection severity. For example, individuals vaccinated BCG protect tuberculosis were also protected from malaria SARS-CoV-2 infections. Epigenetic modifications such histone acetylation metabolic reprogramming (e.g. shift towards glycolysis) their inter-linked regulations are key factors underpinning activation cells. The integrated epigenetic rewiring generates sufficient intermediates, which is crucial meet energy demand required produce proinflammatory antimicrobial responses by These determine efficacy durability immunity. Importantly, signaling pathways regulatory molecules be harnessed potential targets for developing novel intervention strategies, better vaccines immunotherapies infectious (e.g., sepsis) non-infectious cancer) diseases. However, aberrant inflammation caused inappropriate onset lead severe autoimmune pathological consequences, systemic sclerosis granulomatosis). In review, we provide overview conventional adaptive summarize various mechanistic associated regulation immunity, focusing on immunologic, metabolic, changes myeloid This review underscores transformative immunology, paving way therapeutic strategies diseases leverage memory.

Language: Английский

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COVID-19 in Children: Expressions of Type I/II/III Interferons, TRIM28, SETDB1, and Endogenous Retroviruses in Mild and Severe Cases

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(14), P. 7481 - 7481

Published: July 13, 2021

Children with the new coronavirus disease 2019 (COVID-19) have milder symptoms and a better prognosis than adult patients. Several investigations assessed type I, II, III interferon (IFN) signatures in SARS-CoV-2 infected adults, however no data are available for pediatric TRIM28 SETDB1 regulate transcription of multiple genes involved immune response as well human endogenous retroviruses (HERVs). Exogenous viral infections can trigger activation HERVs, which turn induce inflammatory reactions. Despite potential cross-talks between infection TRIM28, SETDB1, information on their expressions COVID-19 patients is lacking. We assessed, through PCR real time Taqman amplification assay, levels six IFN-I stimulated genes, IFN-II three its sensitive IFN-lIIs, pol HERV-H, -K, -W families, env Syncytin (SYN)1, SYN2, sclerosis-associated retrovirus (MRSV) peripheral blood from children control uninfected subjects. Higher expression inducible were observed 36 mild or moderate compared to controls, whereas concentrations decreased 17 severe 11 multisystem syndrome (MIS-C). Similar findings found TRIM-28, every HERV gene. Positive correlations emerged transcriptional I II IFNs, HERVs IFN-III comparable each group This preserved induction IFN-λs could contribute whom deficiency has been reported. The upregulation IFN-I, IFN-II, symptoms, declines cases MIS-C, positive SARS-CoV-2-infected suggest that they may play important roles conditioning evolution infection.

Language: Английский

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Maternal diet alters long-term innate immune cell memory in fetal and juvenile hematopoietic stem and progenitor cells in nonhuman primate offspring

Cell Reports, Journal Year: 2023, Volume and Issue: 42(4), P. 112393 - 112393

Published: April 1, 2023

Maternal overnutrition increases inflammatory and metabolic disease risk in postnatal offspring. This constitutes a major public health concern due to increasing prevalence of these diseases, yet mechanisms remain unclear. Here, using nonhuman primate models, we show that maternal Western-style diet (mWSD) exposure is associated with persistent pro-inflammatory phenotypes at the transcriptional, metabolic, functional levels bone marrow-derived macrophages (BMDMs) from 3-year-old juvenile offspring hematopoietic stem progenitor cells (HSPCs) fetal marrow liver. mWSD also increased oleic acid Assay for transposase-accessible chromatin sequencing (ATAC-seq) profiling HSPCs BMDMs mWSD-exposed juveniles supports model which transmit memory myeloid beginning utero. These findings alters long-term immune cell developmental programming proposed consequences chronic diseases featuring altered immune/inflammatory activation across lifespan.

Language: Английский

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Trained Immunity Contribution to Autoimmune and Inflammatory Disorders

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: April 8, 2022

A dysregulated immune response toward self-antigens characterizes autoimmune and autoinflammatory (AIF) disorders. Autoantibodies or autoreactive T cells contribute to diseases, while autoinflammation results from a hyper-functional innate system. Aside their differences, many studies suggest that monocytes macrophages (Mo/Ma) significantly the development of both types disease. Mo/Ma are promote an immune-modulatory, pro-inflammatory, repair depending on microenvironment. However, understanding contribution these different disorders has been difficult due high functional phenotypic plasticity. Several factors can influence function under landscape autoimmune/autoinflammatory such as genetic predisposition, epigenetic changes, infections. For instance, some vaccines microorganisms induce changes in Mo/Ma, modifying responses. This phenomenon is known trained immunity. Trained immunity be mediated by NK independently B cell function. It defined altered same during second encounter. The improvement related metabolic modify gene expression. Although benefits training have highlighted vaccination context, effects this type autoimmunity chronic inflammation still remain controversial. Induction reprograms cellular metabolism hematopoietic stem (HSCs), transmitting memory-like phenotype cells. Thus, derived HSCs typically present shift glycolysis, which leads modification chromatin architecture. During immunity, facilitate specific expression after secondary challenge with other stimuli. Consequently, enhanced pro-inflammatory could developing maintaining diseases. prediction outcome not simple, propose beneficial AIF conditions inducing anti-inflammatory article describes mechanisms involved affect contraposing controversial evidence how it may impact autoimmune/autoinflammation conditions.

Language: Английский

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Toll-like receptor 9 deficiency induces osteoclastic bone loss via gut microbiota-associated systemic chronic inflammation

Bone Research, Journal Year: 2022, Volume and Issue: 10(1)

Published: May 27, 2022

Toll-like receptors (TLRs) play pivotal roles in inflammation and provide important links between the immune skeletal systems. Although activation of TLRs may affect osteoclast differentiation bone metabolism, whether how are required for normal remodeling remains to be fully explored. In current study, we show first time that TLR9-/- mice exhibit a low mass low-grade systemic chronic inflammation, which is characterized by expansion CD4+ T cells increased levels inflammatory cytokines, including TNFα, RANKL, IL1β. The these cytokines significantly promote osteoclastogenesis induce loss. Importantly, TLR9 deletion alters gut microbiota, this dysbiosis basis loss observed mice. Furthermore, through single-cell RNA sequencing, identified myeloid-biased hematopoiesis marrow determined increase myelopoiesis, likely caused adaptation hematopoietic stem also contributes inflammation-induced subsequent Thus, our study provides novel evidence signaling connects system, critical maintaining homeostasis hematopoiesis, metabolism under conditions.

Language: Английский

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Epigenetic adjuvants: durable reprogramming of the innate immune system with adjuvants

Current Opinion in Immunology, Journal Year: 2022, Volume and Issue: 77, P. 102189 - 102189

Published: May 16, 2022

Language: Английский

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