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

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

• Publication year

  2023

• Venue

  Frontiers in Immunology

• Publication date

  2023-03-13

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3389/fimmu.2023.1147476PMID 36993966PMCID 10040606
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Lack of evidence for intergenerational inheritance of immune resistance to infections

  2022cited by this paper
• Innate antiviral immunity: how prior exposures can guide future responses.

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• Helminth Glycans at the Host-Parasite Interface and Their Potential for Developing Novel Therapeutics

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• Remote regulation of type 2 immunity by intestinal parasites.

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• TSLP-Driven Chromatin Remodeling and Trained Systemic Immunity after Neonatal Respiratory Viral Infection

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• Transmission of trained immunity and heterologous resistance to infections across generations

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• Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart

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• Continuous Exposure to Non-Soluble β-Glucans Induces Trained Immunity in M-CSF-Differentiated Macrophages

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• Tick host immunity: vector immunomodulation and acquired tick resistance.

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• Immunological memory in rheumatic inflammation — a roadblock to tolerance induction

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• Trained Innate Immunity Induced by Vaccination with Low-Virulence Candida Species Mediates Protection against Several Forms of Fungal Sepsis via Ly6G+ Gr-1+ Leukocytes

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• Innate Immune Memory in Hematopoietic Stem/Progenitor Cells: Myeloid-Biased Differentiation and the Role of Interferon

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• Vaccination induces rapid protection against bacterial pneumonia via training alveolar macrophage in mice

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• Optimize Prime/Boost Vaccine Strategies: Trained Immunity as a New Player in the Game

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• Induction of trained immunity by influenza vaccination - impact on COVID-19

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• Household Contacts of Leprosy Patients in Endemic Areas Display a Specific Innate Immunity Profile

  2020cited by this paper
• Immunometabolic control of trained immunity

  2020cited by this paper
• Trained immunity and host‐pathogen interactions

  2020cited by this paper
• β-Glucan as Trained Immunity-Based Adjuvants for Rabies Vaccines in Dogs

  2020cited by this paper
• Airway immunometabolites fuel Pseudomonas aeruginosa infection

  2020cited by this paper
• Trained immunity, tolerance, priming and differentiation: distinct immunological processes

  2020cited by this paper
• Immunotherapeutic Potential of Interleukin-32 and Trained Immunity for Leishmaniasis Treatment.

  2020cited by this paper
• M. tuberculosis Reprograms Hematopoietic Stem Cells to Limit Myelopoiesis and Impair Trained Immunity

  2020cited by this paper
• The Intersection of Epigenetics and Metabolism in Trained Immunity.

  2020cited by this paper
• Innate Immune Memory to Repeated Borrelia burgdorferi Exposure Correlates with Murine In Vivo Inflammatory Phenotypes

  2020cited by this paper
• Pre-exposure to Candida glabrata protects Galleria mellonella against subsequent lethal fungal infections

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• Early-Life Respiratory Syncytial Virus Infection, Trained Immunity and Subsequent Pulmonary Diseases

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• Could BCG Vaccination Induce Protective Trained Immunity for SARS-CoV-2?

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• Targeting Natural Killer Cells for Improved Immunity and Control of the Adaptive Immune Response

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• Pseudomonas aeruginosa Utilizes Host-Derived Itaconate to Redirect Its Metabolism to Promote Biofilm Formation.

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• Trained Immunity: a Tool for Reducing Susceptibility to and the Severity of SARS-CoV-2 Infection

  2020influential reference
• AIDS-Related Mycoses: Updated Progress and Future Priorities.

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• Oat-Derived β-Glucans Induced Trained Immunity Through Metabolic Reprogramming

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• Pulmonary Pathogens Adapt to Immune Signaling Metabolites in the Airway

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• Defining trained immunity and its role in health and disease

  2020influential reference
• Myeloid Cell-Mediated Trained Innate Immunity in Mucosal AIDS Vaccine Development

  2020cited by this paper
• Identification of a Neisseria gonorrhoeae Histone Deacetylase: Epigenetic Impact on Host Gene Expression

  2020cited by this paper
• Uric acid pathway activation during Respiratory virus infection promotes Th2 immune responses via innate cytokine production and ILC2 accumulation

  2020cited by this paper
• β-Glucan Induces Protective Trained Immunity against Mycobacterium tuberculosis Infection: A Key Role for IL-1

  2020cited by this paper
• Buruli ulcer: The Efficacy of Innate Immune Defense May Be a Key Determinant for the Outcome of Infection With Mycobacterium ulcerans

  2020cited by this paper
• Overcoming immune dysfunction in the elderly: trained immunity as a novel approach

  2020cited by this paper
• INTERACTING NON-SPECIFIC IMMUNOLOGICAL EFFECTS OF BCG AND Tdapf VACCINATIONS: AN EXPLORATIVE RANDOMIZED TRIAL.

  2019cited by this paper
• The Itaconate Pathway Is a Central Regulatory Node Linking Innate Immune Tolerance and Trained Immunity.

  2019cited by this paper
• Innate and Adaptive Immune Memory: an Evolutionary Continuum in the Host's Response to Pathogens.

  2019cited by this paper
• Adaptive immune responses to primary and secondary dengue virus infections

  2019cited by this paper
• Disease Tolerance as an Inherent Component of Immunity.

  2019cited by this paper
• Nonspecific effects of oral vaccination with live-attenuated Salmonella Typhi strain Ty21a

  2019cited by this paper
• Genetic defects in fungal recognition and susceptibility to invasive pulmonary aspergillosis.

  2019cited by this paper
• Sex-associated TSLP-induced immune alterations following early-life RSV infection leads to enhanced allergic disease

  2019cited by this paper
• Spectrum of Trained Innate Immunity Induced by Low-Virulence Candida Species against Lethal Polymicrobial Intra-abdominal Infection

  2019cited by this paper
• Anti-inflammatory Trained Immunity Mediated by Helminth Products Attenuates the Induction of T Cell-Mediated Autoimmune Disease

  2019cited by this paper
• Japanese Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices

  2019cited by this paper
• Metabolic Adaptation in Methicillin-Resistant Staphylococcus aureus Pneumonia

  2019cited by this paper
• Strains of Staphylococcus aureus that Colonize and Infect Skin Harbor Mutations in Metabolic Genes

  2019cited by this paper
• β-Glucan-Induced Trained Immunity Protects against Leishmania braziliensis Infection: a Crucial Role for IL-32.

  2019cited by this paper
• Staphylococcus aureus small colony variants impair host immunity by activating host cell glycolysis and inducing necroptosis

  2019cited by this paper
• Early Protection against Pertussis Induced by Live Attenuated Bordetella pertussis BPZE1 Depends on TLR4

  2019cited by this paper
• A Heat-Killed Cryptococcus Mutant Strain Induces Host Protection against Multiple Invasive Mycoses in a Murine Vaccine Model

  2019cited by this paper
• BCG-Induced Cross-Protection and Development of Trained Immunity: Implication for Vaccine Design

  2019cited by this paper
• The Case for an Expanded Concept of Trained Immunity

  2018cited by this paper
• Evidence of Increase in Mortality After the Introduction of Diphtheria–Tetanus–Pertussis Vaccine to Children Aged 6–35 Months in Guinea-Bissau: A Time for Reflection?

  2018cited by this paper
• Regulation of Endotoxin Tolerance and Compensatory Anti-inflammatory Response Syndrome by Non-coding RNAs

  2018cited by this paper
• Faculty Opinions recommendation of BCG Educates Hematopoietic Stem Cells to Generate Protective Innate Immunity against Tuberculosis.

  2018cited by this paper
• Malaria prevention: from immunological concepts to effective vaccines and protective antibodies

  2018cited by this paper
• BCG Educates Hematopoietic Stem Cells to Generate Protective Innate Immunity against Tuberculosis.

  2018cited by this paper
• Cutting Edge: Plasmodium falciparum Induces Trained Innate Immunity

  2018cited by this paper
• Climate Change and the Neglected Tropical Diseases

  2018cited by this paper
• Helminth Immunomodulation in Autoimmune Disease

  2017cited by this paper
• Brave New Worlds: The Expanding Universe of Lyme Disease

  2017cited by this paper
• Epigenetics and Trained Immunity

  2017cited by this paper
• Effect of Early‐Life Geohelminth Infections on the Development of Wheezing at 5 Years of Age

  2017cited by this paper
• Parasitic helminth infections and the control of human allergic and autoimmune disorders.

  2016cited by this paper
• Trained immunity: A program of innate immune memory in health and disease

  2016cited by this paper
• Helminth Products Protect against Autoimmunity via Innate Type 2 Cytokines IL-5 and IL-33, Which Promote Eosinophilia

  2016cited by this paper
• Mycobacterium leprae Activates Toll-Like Receptor-4 Signaling and Expression on Macrophages Depending on Previous Bacillus Calmette-Guerin Vaccination

  2016cited by this paper
• Resource Host and Environmental Factors Influencing Individual Human Cytokine Responses Graphical

  2016cited by this paper
• Dengue infection

  2016cited by this paper
• Fibroblasts profiling in scarring trachoma identifies IL-6 as a functional component of a fibroblast-macrophage pro-fibrotic and pro-inflammatory feedback loop

  2016cited by this paper
• Toll‐like receptor signaling in primary immune deficiencies

  2015cited by this paper
• Efficacy and Long-Term Safety of a Dengue Vaccine in Regions of Endemic Disease.

  2015cited by this paper
• Global Estimates of the Prevalence and Incidence of Four Curable Sexually Transmitted Infections in 2012 Based on Systematic Review and Global Reporting

  2015cited by this paper
• Trained immunity in newborn infants of HBV-infected mothers

  2015influential reference
• Trained innate immunity as underlying mechanism for the long‐term, nonspecific effects of vaccines

  2015cited by this paper
• Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity

  2014cited by this paper
• Trained Immunity or Tolerance: Opposing Functional Programs Induced in Human Monocytes after Engagement of Various Pattern Recognition Receptors

  2014cited by this paper
• Limited Type I Interferons and Plasmacytoid Dendritic Cells during Neonatal Respiratory Syncytial Virus Infection Permit Immunopathogenesis upon Reinfection

  2014cited by this paper
• Innate sensing of malaria parasites

  2014cited by this paper
• Bacterial itaconate degradation promotes pathogenicity.

  2014cited by this paper
• Acinetobacter baumannii nosocomial infections.

  2013cited by this paper
• Immune Responsive Gene 1 (IRG1) Promotes Endotoxin Tolerance by Increasing A20 Expression in Macrophages through Reactive Oxygen Species*

  2013cited by this paper
• Respiratory Syncytial Virus—A Comprehensive Review

  2013cited by this paper
• An Overview of Fungal Infections

  2012cited by this paper
• Introduction to Helminth Infections

  2012cited by this paper
• Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes.

  2012cited by this paper
• Bacille Calmette-Guérin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes

  2012cited by this paper
• Lyme disease: review

  2012cited by this paper
• Endothelial Cells Elicit Immune-Enhancing Responses to Dengue Virus Infection

  2012cited by this paper
• Disease Tolerance as a Defense Strategy

  2012cited by this paper
• Saving lives by training innate immunity with bacille Calmette-Guérin vaccine

  2012cited by this paper

• A Revolutionary Concept in Innate Immunity and its Implications for Vaccine Development and Immune Therapies: A Comprehensive Review of Trained Immunity

  2026cites this paper
• Potential Non-Specific Benefits of Seasonal Influenza Vaccination: Evidence, Knowledge Gaps, and Future Directions

  2026cites this paper
• Non-antibiotic Treatments for Pneumonia Host-Directed Therapies, Next-Steps and Future Directions

  2026cites this paper
• Children's immunity under environmental pressure

  2025cites this paper
• Rapid Natural Killer Cell Gene Responses, Generated by TLR Ligand-Induced Trained Immunity, Provide Protection to Bacterial Infection in rag1−/− Mutant Zebrafish (Danio rerio)

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• Trained immunity in chronic inflammatory diseases and cancer

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• A mode of action protein based approach that characterizes the relationships among most major diseases

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• Advocating the role of trained immunity in the pathogenesis of ME/CFS: a mini review

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• Oral and transdermal administration of lipopolysaccharide safely enhances self-healing ability through the macrophage network

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• Succinate contributes to Staphylococcus aureus skin infection by reactive oxygen species-hypoxic inducible factor 1α-glycolysis axis.

  2025cites this paper
• In-ovo stimulation trains innate immunity to mitigate Campylobacter jejuni in broiler chickens

  2025cites this paper
• EVOLUTION OF CLINICAL MANIFESTATIONS OF WHOOPING COUGH IN CHILDREN IN THE POST-COVID-19 PANDEMIC PERIOD

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• Targeting alveolar macrophages in tuberculosis: Exploiting trained immunity for novel therapeutic approaches.

  2025cites this paper
• Trained immunity in farm animals

  2025influential citation
• Changes in Neutrophil-to-Lymphocyte Ratio (NLR) in patients with low-grade Squamous Intraepithelial Lesions after Coriolus versicolor vaginal gel intervention

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• Recent Advances of Trained immunity in Macrophages

  2025cites this paper
• Divergent metabolic rewiring shapes altered innate immunity.

  2025cites this paper
• Innate immune molecular landscape following controlled human influenza virus infection.

  2025cites this paper
• The innate immune response in SARS-CoV2 infection: focus on toll-like receptor 4 in severe disease outcomes

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• Cross-reactivity and protective efficacy of antibodies raised to BamA for broad-spectrum antimicrobial resistant Acinetobacter baumannii

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• The Neutrophil-to-Albumin Ratio (NAR) Reflects the Severity of the Post-CABG Inflammatory Response and Is Associated with a Pre-Existing Pro-Inflammatory Monocyte Profile

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• Trajectories of prematurity-associated lung disease: lifelong lung health.

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• A nano-vaccine strategy for combatting implant-associated biofilm infections

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• From Methylomes to CRISPR Epigenetic Editing: New Paths in Antibiotic Resistance

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• Trained Immunity: RoadMap for drug discovery and development

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• Role of Trained Immunity in Heath and Disease

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• Advancing veterinary vaccines design through trained immunity insights

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• Trained Innate Immunity in Animal Models of Cardiovascular Diseases

  2024cites this paper
• Innate Immune Training in Chickens for Improved Defense against Pathogens: A Review

  2024cites this paper
• Metabolic regulation of the host-fungus interaction: from biological principles to therapeutic opportunities.

  2024cites this paper
• Vaccines Induce Homeostatic Immunity, Generating Several Secondary Benefits

  2024cites this paper
• The causes and consequences of trained immunity in myeloid cells

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• Emerging Approaches for Mitigating Biofilm-Formation-Associated Infections in Farm, Wild, and Companion Animals

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• The potency of hematopoietic stem cell reprogramming for changing immune tone

  2024cites this paper
• Protective Effects from Prior Pneumococcal Vaccination in Patients with Chronic Airway Diseases during Hospitalization for Influenza—A Territory-Wide Study

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• Adjuvant system AS01: from mode of action to effective vaccines

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• Mucosal Immunity and Trained Innate Immunity of the Gut

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• The microbial damage and host response framework: lesson learned from pathogenic survival trajectories and immunoinflammatory responses of Talaromyces marneffei infection

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• Trained immunity: a revolutionary immunotherapeutic approach

  2024cites this paper
• Features of Gene Regulation in Violation of the Inflammatory Response of Monocyte-like Cells Bearing Mitochondrial Mutations Associated with Atherosclerosis

  2024cites this paper
• Innate immune epigenomic landscape following controlled human influenza virus infection

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• Netosis and trained immunity in tick-borne diseases: a possible pathogenetic role.

  2024cites this paper
• Innate lymphoid cells and infectious diseases

  2024cites this paper
• Mexican Delphi Consensus For Use Immunotherapy With MV130 Vaccine In Patients With Recurrent Respiratory Infectious Diseases (Expert Panel)

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• Alleviation of monocyte exhaustion by BCG derivative mycolic acid

  2024cites this paper
• Agonistic effect of peptides derived from a truncated HMGB1 acidic tail sequence in TLR5 from Salmo salar.

  2023cites this paper
• Mucosal recombinant BCG vaccine induces lung-resident memory macrophages and enhances trained immunity via mTORC2/HK1-mediated metabolic rewiring

  2023cites this paper
• Exploring the Immune Response against RSV and SARS-CoV-2 Infection in Children

  2023cites this paper