Signal-Strength and History-Dependent Innate Immune Memory Dynamics in Health and Disease

2021 ◽  
Author(s):  
Shuo Geng ◽  
Kisha Pradhan ◽  
Liwu Li
Keyword(s):  
Signal Strength ◽  
Innate Immune ◽  
Immune Memory ◽  
Health And Disease

scholarly journals The Role of Cell Metabolism in Innate Immune Memory

2020 ◽  
pp. 1-9
Author(s):  
Anaisa Valido Ferreira ◽  
Jorge Domiguéz-Andrés ◽  
Mihai Gheorghe Netea
Keyword(s):  
Metabolic Pathways ◽  
Tricarboxylic Acid Cycle ◽  
Cell Metabolism ◽  
Innate Immune ◽  
Immune Memory ◽  
Functional Changes ◽  
Trained Immunity ◽  
Health And Disease

Immunological memory is classically attributed to adaptive immune responses, but recent studies have shown that challenged innate immune cells can display long-term functional changes that increase nonspecific responsiveness to subsequent infections. This phenomenon, coined <i>trained immunity</i> or <i>innate immune memory</i>, is based on the epigenetic reprogramming and the rewiring of intracellular metabolic pathways. Here, we review the different metabolic pathways that are modulated in trained immunity. Glycolysis, oxidative phosphorylation, the tricarboxylic acid cycle, amino acid, and lipid metabolism are interplaying pathways that are crucial for the establishment of innate immune memory. Unraveling this metabolic wiring allows for a better understanding of innate immune contribution to health and disease. These insights may open avenues for the development of future therapies that aim to harness or dampen the power of the innate immune response.

scholarly journals Trained immunity: A program of innate immune memory in health and disease

Science ◽  
2016 ◽  
Vol 352 (6284) ◽  
pp. aaf1098-aaf1098 ◽  
Author(s):  
M. G. Netea ◽  
L. A. B. Joosten ◽  
E. Latz ◽  
K. H. G. Mills ◽  
G. Natoli ◽  
...  
Keyword(s):  
Innate Immune ◽  
Immune Memory ◽  
Trained Immunity ◽  
Health And Disease

scholarly journals Trained Immunity at a Glance; A Review on the Innate Immune Memory and its Potential Role in Infections, Diseases and New Therapeutic Strategies

2020 ◽  
Vol 8 (1) ◽  
pp. 68-81
Author(s):  
Silvia Incalcaterra ◽  
Jorge Andres Dominguez
Keyword(s):  
Therapeutic Strategies ◽  
Innate Immune ◽  
Immune Memory ◽  
Therapeutic Approaches ◽  
Trained Immunity ◽  
Adaptive Immune ◽  
Specific Memory ◽  
Health And Disease ◽  
The Impact ◽  
Infections Diseases

Despite the existence of two different branches of immunity, innate and adaptive, it has been described that both systems are characterized by the establishment of memory responses. Indeed, it has been shown that cells belonging to the innate immune system can express a so-called “trained” memory, although it has different features from the adaptive immune memory. Adaptive memory is a long-lasting specific memory whereas innate memory involves non-specific responses which enhance the immune response during a second reinfection. However, many aspects of the trained immunity are still unclear. Metabolic and epigenetic reprogramming have been pointed as the two processes responsible for the establishment of the innate memory. Trained immunity seems to be responsible for the heterologous effect of many vaccines such as BCG, thus giving insights for the development of new therapies. Although its potential beneficial role, trained immunity could also have detrimental effects that might worsen the progress of certain diseases. The purpose of this literature review is to provide an in-depth review on the major characteristics of trained immunity, describing the main pathways at the basis of the evolution and establishment of memory in innate cells. In addition, the present review assesses the modern evidence of the impact of trained immunity in health and disease, strengthening the hypotheses that this innate memory may be considered both in the formulation of new therapeutic strategies and in the current therapeutic approaches.

scholarly journals Possible contribution of trained immunity in faulty hormonal imprinting and DOHaD: Review and hypothesis

2020 ◽  
Author(s):  
György Csaba
Keyword(s):  
Animal Experiments ◽  
Innate Immune ◽  
Immune Memory ◽  
Early Adversity ◽  
Hormonal Imprinting ◽  
Adult Age ◽  
Adaptive Immune ◽  
Base Sequences ◽  
Long Time ◽  
Health And Disease

AbstractThe faulty hormonal imprinting theory (published in 1980) and the DOHaD (Developmental Origin of Health and Disease theory (published in 1986) are twin-concepts: both justify the manifestation after long time (in adults) diseases which had been provoked in differentiating cells (e.g. during gestation). This was demonstrated using animal experiments as well, as comparative statistical methods (in human cases). However, there is no explanation for the tools of memorization (even after decades) of the early adversity and the tools of execution (manifestation) in adult age. It seems likely that immune memory is involved to the memorization of early adversity, up to the manifestation of the result (non-communicable diseases). Nevertheless, the relatively short timespan of adaptive immune memory makes this system insuitable for this function, however the newly recognized trained memory of the innate immune system seems to be theoretically suitable for the storage of the records and handling the sequalae, which is the epigenetic reprogramming in the time of provocation, without changes in base sequences (mutation). The flawed (damaged) program is manifested later, in adult age. Evidences are incomplete, so further animal experiments and human observations are needed for justifying the theory.

Innate immune memory mediates increased susceptibility to Alzheimeŕs disease-like pathology in sepsis surviving mice

2021 ◽  
Author(s):  
Virginia L. De Sousa ◽  
Suzana B. Araújo ◽  
Leticia M. Antonio ◽  
Mariana Silva-Queiroz ◽  
Lilian C. Colodeti ◽  
...  
Keyword(s):  
Innate Immune ◽  
Immune Memory ◽  
Alzheimers Disease ◽  
Increased Susceptibility

scholarly journals The Role of the Pathogen Dose and PI3Kγ in Immunometabolic Reprogramming of Microglia for Innate Immune Memory

2021 ◽  
Vol 22 (5) ◽  
pp. 2578
Author(s):  
Trim Lajqi ◽  
Christian Marx ◽  
Hannes Hudalla ◽  
Fabienne Haas ◽  
Silke Große ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Immune Tolerance ◽  
Immune Cells ◽  
Low Dose ◽  
Innate Immune ◽  
Immune Memory ◽  
Innate Immune Cells ◽  
Atp Production ◽  
Dose Dependent

Microglia, the innate immune cells of the CNS, exhibit long-term response changes indicative of innate immune memory (IIM). Our previous studies revealed IIM patterns of microglia with opposing immune phenotypes: trained immunity after a low dose and immune tolerance after a high dose challenge with pathogen-associated molecular patterns (PAMP). Compelling evidence shows that innate immune cells adopt features of IIM via immunometabolic control. However, immunometabolic reprogramming involved in the regulation of IIM in microglia has not been fully addressed. Here, we evaluated the impact of dose-dependent microglial priming with ultra-low (ULP, 1 fg/mL) and high (HP, 100 ng/mL) lipopolysaccharide (LPS) doses on immunometabolic rewiring. Furthermore, we addressed the role of PI3Kγ on immunometabolic control using naïve primary microglia derived from newborn wild-type mice, PI3Kγ-deficient mice and mice carrying a targeted mutation causing loss of lipid kinase activity. We found that ULP-induced IIM triggered an enhancement of oxygen consumption and ATP production. In contrast, HP was followed by suppressed oxygen consumption and glycolytic activity indicative of immune tolerance. PI3Kγ inhibited glycolysis due to modulation of cAMP-dependent pathways. However, no impact of specific PI3Kγ signaling on immunometabolic rewiring due to dose-dependent LPS priming was detected. In conclusion, immunometabolic reprogramming of microglia is involved in IIM in a dose-dependent manner via the glycolytic pathway, oxygen consumption and ATP production: ULP (ultra-low-dose priming) increases it, while HP reduces it.

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