Trained Immunity: Reprogramming Innate Immunity in Health and Disease

2021 ◽  
Vol 39 (1) ◽  
pp. 667-693 ◽  
Author(s):  
Siroon Bekkering ◽  
Jorge Domínguez-Andrés ◽  
Leo A.B. Joosten ◽  
Niels P. Riksen ◽  
Mihai G. Netea
Keyword(s):  
Innate Immune ◽  
Autoinflammatory Syndromes ◽  
Trained Immunity ◽  
Adaptive Immune ◽  
Inflammatory Conditions ◽  
Current State ◽  
Secondary Infections ◽  
Health And Disease ◽  
Adaptive Immune Systems ◽  
Memory Characteristics

Traditionally, the innate and adaptive immune systems are differentiated by their specificity and memory capacity. In recent years, however, this paradigm has shifted: Cells of the innate immune system appear to be able to gain memory characteristics after transient stimulation, resulting in an enhanced response upon secondary challenge. This phenomenon has been called trained immunity. Trained immunity is characterized by nonspecific increased responsiveness, mediated via extensive metabolic and epigenetic reprogramming. Trained immunity explains the heterologous effects of vaccines, which result in increased protection against secondary infections. However, in chronic inflammatory conditions, trained immunity can induce maladaptive effects and contribute to hyperinflammation and progression of cardiovascular disease, autoinflammatory syndromes, and neuroinflammation. In this review we summarize the current state of the field of trained immunity, its mechanisms, and its roles in both 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 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 Lessons from Bacillus Calmette-Guérin: Harnessing Trained Immunity for Vaccine Development

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2109
Author(s):  
Samuel T. Pasco ◽  
Juan Anguita
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Vaccine Development ◽  
Vaccine Design ◽  
Innate Immune ◽  
Bacillus Calmette Guerin ◽  
Adaptive Immune Responses ◽  
Trained Immunity ◽  
Adaptive Immune ◽  
Potential Methods

Vaccine design traditionally focuses on inducing adaptive immune responses against a sole target pathogen. Considering that many microbes evade innate immune mechanisms to initiate infection, and in light of the discovery of epigenetically mediated innate immune training, the paradigm of vaccine design has the potential to change. The Bacillus Calmette-Guérin (BCG) vaccine induces some level of protection against Mycobacterium tuberculosis (Mtb) while stimulating trained immunity that correlates with lower mortality and increased protection against unrelated pathogens. This review will explore BCG-induced trained immunity, including the required pathways to establish this phenotype. Additionally, potential methods to improve or expand BCG trained immunity effects through alternative vaccine delivery and formulation methods will be discussed. Finally, advances in new anti-Mtb vaccines, other antimicrobial uses for BCG, and “innate memory-based vaccines” will be examined.

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 Total Recall: Intestinal TRM Cells in Health and Disease

2021 ◽  
Vol 11 ◽  
Author(s):  
Eva-Maria Paap ◽  
Tanja M. Müller ◽  
Katrin Sommer ◽  
Markus F. Neurath ◽  
Sebastian Zundler
Keyword(s):  
Immune Responses ◽  
Current Knowledge ◽  
Immune Surveillance ◽  
Adaptive Immune ◽  
Inflammatory Conditions ◽  
Mucosal Tissues ◽  
Health And Disease ◽  
Set Up ◽  
Resident Memory T Cells ◽  
Shed Light

Tissue-resident memory T cells (TRM cells) have crucial functions in host defense in mucosal tissues. They provide local adaptive immune surveillance and allow the fast initiation of targeted adaptive immune responses in case of antigen re-exposure. Recently, an aberrant activation in the case of immunologically mediated diseases has been increasingly acknowledged. As the organ with the largest interface to the environment, the gastrointestinal tract faces billions of antigens every day. Tightly balanced processes are necessary to ensure tolerance towards non-hazardous antigens, but to set up a powerful immune response against potentially dangerous ones. In this complex nexus of immune cells and their mediators, TRM cells play a central role and have been shown to promote both physiological and pathological events. In this review, we will summarize the current knowledge on the homeostatic functions of TRM cells and delineate their implication in infection control in the gut. Moreover, we will outline their commitment in immune dysregulation in gastrointestinal chronic inflammatory conditions and shed light on TRM cells as current and potential future therapeutic targets.

scholarly journals The Neutrophil’s Role During Health and Disease

2019 ◽  
Vol 99 (2) ◽  
pp. 1223-1248 ◽  
Author(s):  
Pei Xiong Liew ◽  
Paul Kubes
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Acute Injury ◽  
Complex Cells ◽  
Adaptive Immune ◽  
Inflammatory Processes ◽  
Health And Disease ◽  
Injury And Repair

Neutrophils have always been considered as uncomplicated front-line troopers of the innate immune system equipped with limited proinflammatory duties. Yet recently, the role of the neutrophil has been undergoing a rejuvenation of sorts. Neutrophils are now considered complex cells capable of a significant array of specialized functions, and as an effector of the innate immune response, they are able to regulate many processes such as acute injury and repair, cancer, autoimmunity, and chronic inflammatory processes. Furthermore, evidence exists to indicate that neutrophils also contribute to adaptive immunity by aiding the development of specific adaptive immune responses or guiding the subsequent adaptive immune response. With this revived interest in neutrophils and their many novel functions, it is prudent to review what is currently known about neutrophils and, even more importantly, understand what information is lacking. We discuss the essential features of the neutrophil, from its origins, lifespan, subsets, margination and sequestration of the neutrophil to the death of the neutrophil. We highlight neutrophil recruitment to both infected and injured tissues and outline differences in recruitment of neutrophils between different tissues. Finally, we examine how neutrophils use different mechanisms to either bolster protective immune responses or negatively cause pathological outcomes at different locations.

scholarly journals Impaired function and delayed regeneration of dendritic cells in COVID-19

2021 ◽  
Author(s):  
Elena Winheim ◽  
Linus Rinke ◽  
Konstantin Lutz ◽  
Anna Reischer ◽  
Alexandra Leutbecher ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Severe Disease ◽  
Innate Immune ◽  
Severe Illness ◽  
Adaptive Immune ◽  
Follicular Helper ◽  
Secondary Infections ◽  
Classical Monocytes ◽  
Antibody Secreting Cells

Disease manifestations in COVID-19 range from mild to severe illness associated with a dysregulated innate immune response. Alterations in function and regeneration of dendritic cells (DC) and monocytes may contribute to immunopathology and influence adaptive immune responses in COVID-19 patients. We analyzed circulating DC and monocyte subsets in 65 hospitalized COVID-19 patients with mild/moderate or severe disease from acute disease to recovery and in healthy controls. Persisting reduction of all DC subpopulations was accompanied by an expansion of proliferating Lineage- HLADR+ cells lacking DC markers. Increased frequency of the recently discovered CD163+ CD14+ DC3 subpopulation in patients with more severe disease was associated with systemic inflammation, activated T follicular helper cells, and antibody-secreting cells. Persistent downregulation of CD86 and upregulation of PD-L1 in conventional DC (cDC2 and DC3) and classical monocytes associated with a reduced capacity to stimulate naive CD4+ T cells correlated with disease severity. Long-lasting depletion and functional impairment of DCs and monocytes may have consequences for susceptibility to secondary infections and therapy of COVID-19 patients.

scholarly journals Impaired function and delayed regeneration of dendritic cells in COVID-19

2021 ◽  
Vol 17 (10) ◽  
pp. e1009742
Author(s):  
Elena Winheim ◽  
Linus Rinke ◽  
Konstantin Lutz ◽  
Anna Reischer ◽  
Alexandra Leutbecher ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Severe Disease ◽  
Innate Immune ◽  
Severe Illness ◽  
Adaptive Immune ◽  
Follicular Helper ◽  
Secondary Infections ◽  
Programmed Death ◽  
Classical Monocytes ◽  
Antibody Secreting Cells

Disease manifestations in COVID-19 range from mild to severe illness associated with a dysregulated innate immune response. Alterations in function and regeneration of dendritic cells (DCs) and monocytes may contribute to immunopathology and influence adaptive immune responses in COVID-19 patients. We analyzed circulating DC and monocyte subsets in 65 hospitalized COVID-19 patients with mild/moderate or severe disease from acute illness to recovery and in healthy controls. Persisting reduction of all DC subpopulations was accompanied by an expansion of proliferating Lineage−HLADR+ cells lacking DC markers. Increased frequency of CD163+ CD14+ cells within the recently discovered DC3 subpopulation in patients with more severe disease was associated with systemic inflammation, activated T follicular helper cells, and antibody-secreting cells. Persistent downregulation of CD86 and upregulation of programmed death-ligand 1 (PD-L1) in conventional DCs (cDC2 and DC3) and classical monocytes associated with a reduced capacity to stimulate naïve CD4+ T cells correlated with disease severity. Long-lasting depletion and functional impairment of DCs and monocytes may have consequences for susceptibility to secondary infections and therapy of COVID-19 patients.

Alphaviruses: Host pathogenesis, immune response, and vaccine & treatment updates

2021 ◽  
Vol 102 (8) ◽  
Author(s):  
Israel Guerrero-Arguero ◽  
Claudia M. Tellez-Freitas ◽  
K. Scott Weber ◽  
Bradford K. Berges ◽  
Richard A. Robison ◽  
...  
Keyword(s):  
Signs And Symptoms ◽  
Host Immunity ◽  
Innate Immune ◽  
Interferon Response ◽  
Human Pathogens ◽  
Adaptive Immune ◽  
Vaccine Treatment ◽  
Host Cell Interactions ◽  
Infection Mechanisms ◽  
Adaptive Immune Systems

Human pathogens belonging to the Alphavirus genus, in the Togaviridae family, are transmitted primarily by mosquitoes. The signs and symptoms associated with these viruses include fever and polyarthralgia, defined as joint pain and inflammation, as well as encephalitis. In the last decade, our understanding of the interactions between members of the alphavirus genus and the human host has increased due to the re-appearance of the chikungunya virus (CHIKV) in Asia and Europe, as well as its emergence in the Americas. Alphaviruses affect host immunity through cytokines and the interferon response. Understanding alphavirus interactions with both the innate immune system as well as the various cells in the adaptive immune systems is critical to developing effective therapeutics. In this review, we summarize the latest research on alphavirus-host cell interactions, underlying infection mechanisms, and possible treatments.

Toll‐like receptors: The innate immune receptors with ingenious anti‐ viral paradigm

2013 ◽  
Vol 3 (5) ◽  
pp. 207-213
Author(s):  
Yashpal S. Malik ◽  
Kuldeep Sharma ◽  
Lalit Mohan Jeena ◽  
Naveen Kumar ◽  
Subhankar Sircar ◽  
...  
Keyword(s):  
Innate Immune ◽  
Viral Diseases ◽  
The Novel ◽  
Defence Mechanisms ◽  
Immune Systems ◽  
Adaptive Immune ◽  
Potential Applications ◽  
Therapeutic Protocols ◽  
Molecular Patterns ◽  
Adaptive Immune Systems

The appreciative progress in our understanding of the host defence mechanisms through innate and adaptive immune systems has led us to improve therapeutic protocols through the inflection of immune factors. Amidstplethora of pattern recognition receptors (PRRs), the Toll‐like receptors (TLRs) have received substantial consideration as potential regulator and controller of the immune response through their pathogen‐associated molecular patterns (PAMPs). The finding that endogenous ligands, microbial constituents, synthetic components are recognized by TLRs, raised interest in these receptors as potential targets for the development of new therapies for multiple diseases. The TLRs are among the rare targets which are now a days becoming commercially available for treatment of viral diseases and the success has been achieved with imiquimod (TLR7) for human papilloma/ warts treatment. Numerous other therapeutics targeting the TLRs are under pre‐clinical and clinical trials. The novel advances in TLR research shall expound their functions and prospective therapeutic applications. This review updates the usages of these innate immunomodulators in combating various viral frailtes describing in brief the anti‐viral regimens and their potential applications for safeguarding health of humans as well as animals.

Sign in / Sign up

Export Citation Format

Share Document