







































_____________________________________________________________________________________________________ 
 
*Corresponding author: E-mail: lucyjanefrancisokolie@gmail.com; 
 
Cite as: Janefrancis, Okolie Lucy, Maduka Amuche Stella, Ojeniran Taiwo Paul, Yahaya Imran Umar, Lawal Mustapha, Oniye 
Mariam Masud, and Umar Muhammad Muhsin. 2025. “The Role of Trained Immunity in Protection Against Infectious Diseases: 
Epigenetic Reprogramming and Long-Term Immune Responses”. Asian Journal of Immunology 8 (1):86-96. 
https://doi.org/10.9734/aji/2025/v8i1163. 

 
 

Asian Journal of Immunology 
 
Volume 8, Issue 1, Page 86-96, 2025; Article no.AJI.134904 
 

 
 

 

 

The Role of Trained Immunity in 
Protection against Infectious Diseases: 
Epigenetic Reprogramming and Long-

term Immune Responses 
 

Okolie Lucy Janefrancis a*, Maduka Amuche Stella b, 
Ojeniran Taiwo Paul c, Yahaya Imran Umar d, 

Lawal Mustapha e, Oniye Mariam Masud f 

and Umar Muhammad Muhsin g 

 
a Department of Microbiology, Alex Ekwueme Federal University Ndufu-Alike, Nigeria. 

b Department of Science Education, Nnamdi Azikiwe University Awka, Nigeria. 
c Alex Ekwueme Federal University Teaching Hospital, Abakaliki, Ebonyi State, Nigeria. 

d Department of Biochemistry, Bayero University Kano, Nigeria. 
e Department of Microbiology, Kebbi State University of Science and Technology, Aleiro, Nigeria. 

f Department of Environmental Biology, Kwara State Polytechnic/Science Laboratory Technology, 
Nigeria. 

g Department of Microbiology, Bayero University Kano, Nigeria. 
 

Authors’ contributions  
 

This work was carried out in collaboration among all authors. All authors read and approved the final 
manuscript. 

 
Article Information 

 
DOI: https://doi.org/10.9734/aji/2025/v8i1163  

 
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This journal follows the Advanced Open Peer Review policy. Identity of the Reviewers, Editor(s) and additional Reviewers,  
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Received: 26/02/2025 
Published: 03/05/2025 

 
  

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Janefrancis et al.; Asian J. Immunol., vol. 8, no. 1, pp. 86-96, 2025; Article no.AJI.134904 
 
 

 
87 

 

ABSTRACT 
 

Trained immunity, a concept introduced more than a decade ago, defines the non-specific memory 
capacity of innate immunity by epigenetic and metabolic reprogramming. It involves features of 
epigenetic and metabolic reprogramming of innate immune cells that induce long-term functional 
changes in host defense. This review explores the mechanisms and duration of trained immunity, 
as well as the therapies related to its potential in infectious diseases. A systematic literature search 
was conducted across PubMed, Google Scholar, and Web of Science for studies published 
between 2019 and 2025. Experimental and clinical studies on innate immune memory, epigenetic 
modifications, and metabolic pathways associated with long-term immune responses were selected 
as study criteria. The synthesized data was narratively summarized to assess key themes, including 
molecular mechanisms, sustainability, and translational applications. A total of eight studies were 
included in this review. The findings revealed that trained immunity is mediated by histone 
modifications, metabolic changes, and long-term myelopoiesis. Studies also show that immune 
training has varying durations, with effects lasting from weeks to months. Emerging therapeutic 
strategies will focus on vaccine enhancement, cancer immunotherapy, and sepsis management. 
However, challenges remain, including a lack of clinical validation, incomplete mechanistic 
understanding, and ethical concerns. Trained immunity is a promising approach to 
immunomodulation between innate and adaptive immunity. Future research should aim to conduct 
clinical trials, assess safety, and develop precision medicine approaches to efficiently utilize this 
concept in therapeutic applications. 
 

 
Keywords: Trained immunity; innate immune memory; infectious diseases; metabolic 

reprogramming; epigenetics. 
 

ABBREVIATIONS 
 
BCG : Bacillus Calmette-Guérin 
HAND :HIV-associated Neurocognitive 

Disorders 
lncRNA : Long Non-coding RNA  
MeSH : Medical Subject Headings  
NK : Natural Killer 
PRRs : Pattern Recognition Receptors 
TIIs : Trained Immunity-inducing Agents  
TLR : Toll-like Receptors 
 

1. INTRODUCTION 
 

Trained immunity, referred to as innate immune 
memory, is an inherent capability of innate 
immune cells to mount enhanced response to 
secondary infections after an initial exposure. In 
contrast to adaptive immunity where memory 
cells are antigen-specific, trained immunity relies 
on functional reprogramming of the innate 
immune cells, mainly monocytes, macrophages, 
and natural killer cells by epigenetic and 
metabolic modifications (Dulfer & Domínguez-
Andrés, 2024). This is a phenomenon shown 
previously in invertebrates without an adaptive 
immune system suggesting that innate immune 
memory has provided a fundamental 
evolutionary advantage (Netea et al., 2020). 
Trained immunity has its historical basis as early 
as its prolific documentation in the nonspecific 

protective effects of vaccines. For example, the 
bacillus Calmette-Guérin (BCG) vaccine used for 
tuberculosis has been shown to boost resistance 
to unrelated infections and is contrary to the 
prevailing separation of innate and adaptive 
immunity (Berendsen et al., 2021; Ciarlo et al., 
2020). Further studies have demonstrated that 
long-lasting changes in innate immune function 
can be induced by microbial components like β 
glucans and lipopolysaccharides, mediated by 
epigenetic modifications e.g. histone methylation 
and acetylation in particular to inflammatory 
response gene (Bomans et al., 2018; Sánchez-
Ramón et al., 2018). Trained immunity is 
mediated through changes in metabolism 
including the reprogramming of immune 
progenitor cells from the bone marrow to convert 
to aerobic glycolysis. However, it has been 
shown that histone modifications, such as 
H3K4me3 and H3K27ac, are associated with a 
heightened inflammatory response on reinfection 
(Katzmarski et al., 2021). In addition, evidence 
shows that trained immunity is inherited 
transgenerationally by germ cell epigenetic 
modifications and shapes immune responses in 
the offspring (Kaufmann et al., 2022). 
 
Two differing mechanisms of immunological 
memory, namely trained immunity and adaptive 
immune memory, have a distinct cellular basis, 
specificity, duration, and underlying molecular 



 
 
 
 

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88 

 

 
 

Fig. 1. Conceptual framework of the study 
 
mechanisms. Training immunity involves the 
innate immune cells such as monocytes, 
macrophages, and NK cells, while adaptation 
immune memory is dependent on antigen-
specific T and B lymphocytes which get clonally 
expanded and persist for a long period (Netea et 
al., 2020). In contrast to adaptive immunity, 
which works via highly specific somatically 
revisers in antigen receptors to encounter 
antigens previously exposed, trained immunity 
based on broad Pattern Recognition Receptors 
(PRRs), like toll-like receptors (TLRs), to detect 
conserved microbial components (Mulder et al. 
2019). The length of immune memory is 
otherwise very different in these two systems. 
Adaptive immune memory does persist for years 
or even a lifetime, as the presence of long-lived 
memory T and B cells (Bekkering et al., 2021). 
These epigenetic and metabolic reprogramming 
programs that train immunity tend to be at the 
molecular level and include histone modifications 
and shifts in glycolytic metabolism to enhance 
the responsiveness of innate immune cells to 
reinfection (Saeed et al., 2014). Adaptive 
immune memory, however, is sustained through 
clonal expansion, long-lived plasma cells and 
memory T cells upon receipt of antigens with 
specialized effector functions (Sallusto et al., 
2010). These immune strategies also form an 
important distinction in terms of their evolutionary 
origin. Conserved across the wide spectrum of 
diverse species ranging from plants and 
invertebrates, this ancient type of immunity 
definitely plays a selective role in the host 
defense (Duggan et al., 2023). In contrast to 
adaptive immunity, this is unique to the 

vertebrates and gives highly refined and long-
lasting protection against pathogens (Sun & 
Lanier, 2021). 

 
The aim of this review was to investigate the 
complete analysis of protective mechanisms in 
infectious diseases through the synthesis of 
contemporary evidence on molecular processes 
and duration of effect and therapeutic 
possibilities of trained immunity. Fig. 1 illustrates 
the conceptual framework of the study. 

 
2. METHODOLOGY 
 
2.1 Literature Search Strategy 
 
A comprehensive and systematic literature 
search was conducted to identify relevant studies 
on trained immunity, epigenetic reprogramming, 
and long-term immune responses in the context 
of infectious diseases. The search was 
performed across multiple databases, including 
PubMed, Web of Science, and Google Scholar, 
with a timeframe of 2019 to 2025, ensuring broad 
coverage of biomedical and immunological 
research. The search strategy combined Medical 
Subject Headings (MeSH) terms and keywords 
related to trained immunity, innate immune 
memory, epigenetics, histone modifications, 
metabolic reprogramming, and infectious disease 
protection. Boolean operators (AND, OR) were 
used to refine searches (Table 1), and database-
specific filters like full-text availability, and 
publication date restrictions. This review was not 
registered in PROSPERO. 



 
 
 
 

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89 

 

Table 1. Search String 

 
Combination of Keywords 

(“trained immunity” OR “innate immune memory”) AND (“epigenetic reprogramming” OR “histone modification” 
OR “DNA methylation”) AND (“infectious disease” OR “pathogen defense”) AND (“metabolic shift” OR 
“glycolysis”) 

 
Table 2. Methodology 

 
Theme Method 

Literature search PubMed, Web of Science, Google Scholar 
Keywords “trained immunity,” “epigenetic reprogramming,” “infectious disease,” 

“metabolic reprogramming” 
Timeframe 2019 to 2025 
Selection criteria Peer-reviewed articles of original research published in English. 

Studies that investigated trained immunity and its mechanisms, including 
epigenetic and metabolic changes. 
Research focusing on infectious disease protection through innate immune 
memory. 
Experimental and clinical studies involving humans and relevant animal 
models. 

Data extraction & synthesis Data were extracted using a standardized data extraction form. 
Narrative synthesis approach was used to summarize key findings and 
highlight common themes. 

 
2.2 Selection Criteria 
 
This review was conducted following the 
PRISMA guidelines, and a corresponding 
PRISMA flowchart is included in the results to 
illustrate the study selection process. To ensure 
relevance and quality, the following selection 
criteria were applied: 

 
2.2.1 Inclusion criteria 

 
• Peer-reviewed articles of original 

research published in English. 

• Studies that investigated trained 
immunity and its mechanisms, including 
epigenetic and metabolic changes. 

• Research focusing on infectious disease 
protection through innate immune 
memory. 

• Experimental and clinical studies 
involving humans and relevant animal 
models. 

 
2.2.2 Exclusion criteria 

 
• Studies focusing exclusively on adaptive 

immunity without reference to trained 
immunity. 

• Non-English publications. 

• Opinion pieces, editorials, reviews, and 
conference abstracts without full data. 

2.3 Data Extraction and Synthesis 
 
Search results were screened based on the 
predefined inclusion criteria and data from the 
selected studies were extracted independently by 
two reviewers using a standardized data 
extraction form, capturing the study design, 
population involved, interventions, outcomes, 
and key findings. When there were 
discrepancies, it was resolved through 
consensus. A narrative synthesis was used to 
summarize key findings and highlight common 
themes. 
 

3. RESULTS AND DISCUSSION 
 

3.1 Included Studies 
 

Fig. 2 illustrates the included studies selection 
processes. Eight studies were included in this 
review, after a broad selection and screening of 
205 articles. The studies included were 
conducted between 2019 and 2025, with a 
majority of them employing experimental study 
design. Three of the studies had Histone 
modifications as their mechanism of trained 
immunity while two studies identified epigenetic 
modulation as their trained immunity mechanism. 
Bacterial & viral infections were observed to be 
the most common pathogen context across the 
studies and the duration of immune training was 
long-term. 



 
 
 
 

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90 

 

 
 

Fig. 2. PRISMA flow diagram 
 

3.2 Mechanisms Underlying Trained 
Immunity 

 

Trained immunity is primarily driven by 
epigenetic and metabolic reprogramming, 
enabling innate immune cells to mount enhanced 
responses upon secondary stimulation. Key 
epigenetic mechanisms such as histone 
modifications, DNA methylation and their 
regulation have all been the focus of several 
studies. As an example, Jentho et al. (2021) 
established that heme-trained immunity results in 
heme long-lasting epigenetic remodelling that 
alters myelopoiesis and enhances monocyte 
function. In addition, the Set7 lysine 
methyltransferase regulates oxidative 
phosphorylation plasticity for trained immunity in 
response to β glucan stimulation which was 
previously shown by Keating et al. (2020). 
Additionally, these findings are consistent with 
previous work that demonstrated the importance 
of histone methylation and acetylation of immune 
gene promoters to promote hypercytokinemia on 
secondary T-cell stimulation (Fok et al., 2019). 
Other important drivers of trained immunity are 
metabolic reprogramming; glycolysis, oxidative 
phosphorylation, and lipid metabolism are 
shifted. Hao et al. (2025) stated that metabolic 
adaptations, such as enhanced glycolysis and 
glutaminolysis, have a crucial role in innate 
immune memory. This is in alignment with Rusek 
et al. (2018) who showed that even bacterial and 

viral stimuli, elicit metabolic shifts that sustain 
immune memory. In addition, Salauddin et al. 
(2024) rethink that both shifts from oxidative 
phosphorylation and lipid metabolism are crucial 
for the immune response, so that metabolic 
pathways may be targeted to amplify the 
response. Participation of non-coding RNAs in 
trained immunity has also been recently 
highlighted. In the case of Fok et al. (2019), they 
observed that lncRNAs mediate the crosstalk 
between cellular metabolism and epigenetic 
modifications to modulate innate immune 
reprogramming. This coincides with Abhimanyu 
et al. (2021), who showed that targeting RNA-
based regulatory pathways can reverse the post-
infectious epigenetic-mediated immune 
suppression. Overall, the convergence of 
epigenetic and metabolic reprogramming in the 
form of trained immunity indicates the possibility 
of its therapeutic manipulation. While the reliance 
on antigen-specific lymphocytes for classical 
immunological memory, trained immunity might 
be a broader, non-specific protective mechanism 
that can be used for vaccine development and 
immunotherapy (Hajishengallis et al., 2025). 
 

3.3 Duration and Sustainability of Trained 
Immunity 

 

Trained immunity varies with different 
persistence depending on the stimulus, the 
immune cell type, as well as metabolic and 



 
 
 
 

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Table 3. Findings from Included Studies 
 

Author & 
Year 

Study Objective Study Design Mechanisms of 
Trained Immunity 

Disease/Pathogen 
Context 

Duration of 
Immune 
Training 

Clinical/Translational 
Relevance 

Key Findings 

Abhimanyu 
et al., 2021 

Investigate the 
reversal of post-
infectious immune 
suppression via 
epigenetic 
modifications 

Experimental 
study (in vitro & 
in vivo) 

Epigenetic 
modulation 
through histone 
acetylation 

Bacterial & viral 
infections 

Long-term 
effects 
assessed 

Potential for therapeutic 
reprogramming of immune 
responses 

Identified key 
epigenetic markers 
that can reverse 
immune suppression 
post-infection 

Hao et al., 
2025 

Explore metabolic 
adaptations driving 
innate immune 
memory 

Review of 
metabolic 
pathways 

Glycolysis and 
oxidative 
phosphorylation 
shifts 

Broad infectious 
diseases 

Variable 
depending 
on stimulus 

Identifying metabolic 
targets for 
immunotherapies 

Highlighted the role 
of metabolic rewiring 
in sustaining trained 
immunity 

Jentho et al., 
2021 

Study epigenetic 
modulation in trained 
immunity induced by 
heme 

Experimental 
study (animal 
models) 

Histone 
methylation and 
DNA modifications 

Heme-related 
immune disorders 

Long-
lasting 
(several 
months) 

Potential for improving 
anemia and inflammatory 
conditions 

Demonstrated 
sustained 
myelopoiesis and 
immune adaptation 
via heme exposure 

Xing et al., 
2020 

Examine trained 
immunity in tissue-
resident 
macrophages 

Experimental & 
review 

Epigenetic and 
metabolic 
modifications in 
macrophages 

Respiratory infections Months to 
years 

Implications for vaccine 
strategies 

Proposed a new 
vaccination model 
leveraging trained 
macrophage 
responses 

Fok et al., 
2019 

Investigate lncRNA 
involvement in 
metabolic-epigenetic 
immunity links 

Experimental 
study 

Long non-coding 
RNAs (lncRNAs) 
in immune 
reprogramming 

Bacterial & viral 
infections 

Persistent 
effects 

Possible RNA-based 
immunotherapies 

Found lncRNA-
mediated regulatory 
pathways crucial for 
trained immunity 

 

Table 3 Cont’d 
 

Author & 
Year 

Study Objective Study Design Mechanisms of 
Trained 
Immunity 

Disease/Pathogen 
Context 

Duration of 
Immune 
Training 

Clinical/Translational 
Relevance 

Key Findings 

Wang et al., 
2024 

Explore trained 
immunity’s impact on 
sepsis 

Experimental 
study (animal 
models) 

Histone 
modifications, 
cytokine 
reprogramming 

Sepsis Weeks to 
months 

New therapeutic avenues 
for sepsis management 

Found that trained 
immunity can 
enhance sepsis 
resistance but also 



 
 
 
 

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Author & 
Year 

Study Objective Study Design Mechanisms of 
Trained 
Immunity 

Disease/Pathogen 
Context 

Duration of 
Immune 
Training 

Clinical/Translational 
Relevance 

Key Findings 

risk 
hyperinflammation 

Lajqi et al., 
2024 

Investigate trained 
immunity in pediatric 
infections 

Experimental 
study (pediatric 
models) 

Histone 
modifications, 
cytokine memory 

Pediatric bacterial & 
viral infections 

Months to 
years 

Potential for improving 
pediatric vaccine efficacy 

Found that early-life 
infections induce 
long-lasting immune 
adaptations 

Keating et 
al., 2020 

Examine Set7 
methyltransferase’s 
role in trained 
immunity 

Experimental 
study 

Set7-driven 
oxidative 
phosphorylation 
plasticity 

Fungal infections (β-
glucan exposure) 

Long-term 
metabolic 
imprinting 

Targeting Set7 for trained 
immunity-based therapies 

Identified Set7 as a 
key regulator of 
trained immunity in 
response to β-glucan 



 
 
 
 

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epigenetic adaptations. Several studies show 
that trained immunity can persist from weeks to 
months and for years in some cases. According 
to Jentho et al. (2021), when myeloid progenitors 
are exposed to heme, these epigenetic 
modifications lead to long-term immune 
reprogramming beyond the life span of a single 
immune cell through altered hematopoiesis. As in 
Keating et al (2020), β glucan-induced trained 
immunity can persist for up to several months 
through the sustained effect of changes in 
oxidative phosphorylation and mitochondrial 
function. Recovery of trained immunity also 
depends on repeated exposure to stimuli. By 
repeatedly encountering the same microbes, 
recurrent encounters furthered the training of the 
immune system, keeping it lasting much further 
by continuously reprogramming metabolic and 
epigenetic pathways (Rusek et al., 2018). On the 
other hand, Abhimanyu et al. (2021) reported 
that the longevity of trained immunity is context-
dependent and reversible under 
immunosuppressive conditions. This is further 
corroborated by Capriotti and Klase (2024), who 
demonstrate that trained immunity mechanisms 
break down in chronic HIV infection and are lost 
more quickly than would have been otherwise 
the case. In addition, it has been noted in studies 
that trained immunity persistence is disease 
model-dependent. In sepsis-induced trained 
immunity, metabolic adaptations shown by Hao 
et al. (2025) are transient and come back to 
baseline in a couple of weeks. Hajishengallis et 
al. (2025) demonstrated that chronic 
inflammatory disease would maintain trained 
immunity for extended periods, and they suggest 
a possible role in disease progression. Taken as 
a whole these findings suggest that trained 
immunity can be maintained on a sustained basis 
but its persistence depends on external stimuli 
disease states and the cellular environment. 
Consequently, this opens up the potential for 
vaccine development, as prolonging trained 
immunity from a trained immunity-inducing 
vaccine, could provide wide-spectrum protection 
against infectious diseases (Salauddin et al., 
2024). 
 

3.4 Emerging Therapeutic Strategies 
Leveraging 

 

Recent advancement has highlighted trained 
immunity as a promising avenue for the 
development of new therapeutic strategies for 
the promotion of host defense, modulation of 
chronic inflammatory conditions, and other 
desirable effects by vaccine. Using trained 

immunity inducing agents (TIIs), a class of 
agents including the β-glucan and the cell wall 
component vaccine Bacillus Calmette Guérin 
(BCG) is one of the most actively explored 
approaches to providing general protection 
against infections. BCG vaccination induces 
long-term metabolic and epigenetic 
reprogramming in monocytes and enhanced 
resistance to viral and bacterial pathogens 
beyond tuberculosis (Xing et al., 2020). Wang et 
al. (2024) also suggested that trained immunity-
inducing compounds could be used to strengthen 
innate immune responses and thus help host 
resilience to sepsis. Trained immunity is also a 
target beyond infectious diseases towards 
autoimmune and chronic inflammatory disorders. 
Based on their results, Hajishengallis et al. 
(2025) proposed that the trained monocytes and 
macrophages seem to participate in the 
continuous inflammatory cascade in chronic 
diseases, which makes them potential target of 
immunomodulatory therapies. Lajqi et al. (2024) 
explored pediatric infectious diseases and 
showed that manipulating trained immunity could 
improve immune response in 
immunocompromised children. An additional 
creative aspect is using epigenetic and metabolic 
modulators to control trained immunity in 
therapeutic areas. This led Fok et al. (2019) to 
find that Immune training is driven by long 
noncoding RNAs (lncRNAs) as critical regulators, 
that provide new targets of epigenetic-based 
therapies. Metabolic intervention strategy 
targeting lysine methyltransferase Set7 was also 
found by Keating et al. (2020) to boost trained 
immunity via optimization of mitochondrial 
function. Trained immunity is currently being 
studied as a potential tool for the treatment of 
neuro-inflammatory and chronic infection 
conditions, including HIV-associated 
neurocognitive disorders (HAND). According to 
Capriotti and Klase (2024), trained immunity-
modulating agents might reverse innate immune 
dysfunction in HIV resulting in the restoration of 
immune function. 
 

4. CHALLENGES AND FUTURE 
PERSPECTIVES 

 

Despite all of this interest in trained immunity as 
a therapeutic target, many challenges and 
knowledge gaps remain. The lack of an 
understanding of the long-term consequences of 
trained immunity induction is a major limitation. 
Although many studies have uncovered the links 
between epigenetic and metabolic hallmarks of 
innate immune memory (Keating et al., 2020; 



 
 
 
 

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Fok et al., 2019), how long and whether these 
changes have sustained adverse effects remains 
unknown. It is of particular concern, however, 
how excessive immune activation can lead to 
chronic inflammation or autoimmunity 
(Hajishengallis et al., 2025). In addition, most 
recent research relies on in-vitro models or 
preclinical animal studies without necessary 
translation to human immune responses (Xing et 
al., 2020). With these, rigorous clinical trials for 
validation of the efficacy and safety of trained 
immunity-based interventions are required to 
advance the field. Some of the studies have 
demonstrated that vaccination with Bacillus 
Calmette- Guérin (BCG) and β-glucans may 
promote host defense against heterologous 
infections (Xing et al., 2020; Wang et al., 2024), 
but the results should be confirmed in RCTs for 
various populations. In addition, clinical studies 
should determine what the optimal dosing is and 
when and with what population it does and does 
not respond, as it appears that the effects of 
trained immunity might be affected by age, 
genetics, and metabolic status (Salauddin et al., 
2024). Large-scale trials of trained immunity for 
sepsis, cancer immunotherapy, and chronic 
infections would provide crucial insights into its 
therapeutic potential (Xia et al., 2021; Capriotti & 
Klase (2024). From the perspectives of ethics 
and safety, there are multiple concerns when 
manipulating innate immune memory. Trained 
immunity is antigen non-specific, as opposed to 
adaptive immunity, and therefore carries the risk 
of off-target effects, including inappropriate 
inflammation or immune exhaustion 
(Hajishengallis et al., 2025). Intergenerational 
epigenetic inheritance is also a cause for 
concern since the immune changes could be 
passed on to a generation, with uncertain 
consequences (Fok et al., 2019). Regulatory 
bodies must construct a catalog of clear 
guidelines for the clinical medicines involving 
stimulated immunity, as the use of the agents 
must be both safe and ethically justified, and 
available. To make these possible, tailored 
interdisciplinary research and robust clinical trial 
and oversight will need to be guided toward the 
translation of trained immunity-based strategies 
to practical and sustainable clinical interventions. 
 

5. CONCLUSION 
 

Trained immunity has the potential to 
fundamentally change the field of immunology by 
providing novel information regarding the 
process by which innate immune cells learn a 
memory-like response in the context of 

epigenetic and metabolic reprogramming. It is 
reviewed for its mechanisms, duration, and 
potential for therapy, including how these might 
impact infectious diseases, cancer, as well as 
inflammatory disorders. Emerging strategies in β-
glucan-based immunomodulation and vaccine 
adjuvants are promising, but remain challenging 
due to gaps in mechanistic understanding, the 
need for rigorous clinical validation, and ethical 
dilemmas of immune manipulation. Future 
studies should focus on large size clinical trials, 
individualization of immunomodulatory 
approaches, and policies that can make 
implementation safe and effective. With trained 
immunity, disease prevention and treatment of 
many diseases could make this revolution, 
bridging innate and adaptive immune strategies 
for long-term health benefits. 
 

Data availability: No new datasets were 
generated or analyzed in the current study. 
 

CONCENT AND ETHICAL APPROVAL 
 

It is not applicable 
 

DISCLAIMER (ARTIFICIAL INTELLIGENCE) 
 

Author(s) hereby declare that NO generative AI 
technologies such as Large Language Models 
(ChatGPT, COPILOT, etc.) and text-to-image 
generators have been used during the writing or 
editing of this manuscript.  
 

COMPETING INTERESTS 
 

Authors have declared that no competing 
interests exist. 
 

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