Defining trained immunity and its role in health and disease

Netea, Mihai G.; Domínguez‐Andrés, Jorge; Barreiro, Luis B.; Chavakis, Triantafyllos; Divangahi, Maziar; Fuchs, Elaine; Joosten, Leo A. B.; Meer, J.W.M. van der; Mhlanga, Musa M.; Mulder, Willem J. M.; Riksen, Niels P.; Schlitzer, Andreas; Schultze, Joachim L.; Benn, Christine Stabell; Sun, Joseph C.; Xavier, Ramnik J.; Latz, Eicke

doi:10.1038/s41577-020-0285-6

Cited by 1,514 publications

(1,721 citation statements)

References 190 publications

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“…Trained immunity is the functional re-programming of innate immune cells to a more activated state following initial antigen stimulation (infections or vaccination) through metabolic re-programming (enhanced Kreb's cycle) and epigenetic changes (acetylation and demethylation leading to enhanced transcription of IL-1β, IL-6 and TNF-α genes). It can affect progenitor cells of myeloid and monocyte cell lines as well as local cells (lung macrophages and dendritic cells) [54].…”

Section: Trained Immunitymentioning

confidence: 99%

Pathophysiology of COVID-19: Why Children Fare Better than Adults?

et al. 2020

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The world is facing Coronavirus Disease-2019 (COVID-19) pandemic, which is causing a large number of deaths and burden on intensive care facilities. It is caused by Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) originating in Wuhan, China. It has been seen that fewer children contract COVID-19 and among infected, children have less severe disease. Insights in pathophysiological mechanisms of less severity in children could be important for devising therapeutics for high-risk adults and elderly. Early closing of schools and day-care centers led to less frequent exposure and hence, lower infection rate in children. The expression of primary target receptor for SARS-CoV-2, i.e. angiotensin converting enzyme-2 (ACE-2), decreases with age. ACE-2 has lung protective effects by limiting angiotensin-2 mediated pulmonary capillary leak and inflammation. Severe COVID-19 disease is associated with high and persistent viral loads in adults. Children have strong innate immune response due to trained immunity (secondary to live-vaccines and frequent viral infections), leading to probably early control of infection at the site of entry. Adult patients show suppressed adaptive immunity and dysfunctional over-active innate immune response in severe infections, which is not seen in children. These could be related to immune-senescence in elderly. Excellent regeneration capacity of pediatric alveolar epithelium may be contributing to early recovery from COVID-19. Children, less frequently, have risk factors such as co-morbidities, smoking, and obesity. But young infants and children with pre-existing illnesses could be high risk groups and need careful monitoring. Studies describing immune-pathogenesis in COVID-19 are lacking in children and need urgent attention.

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Section: Trained Immunitymentioning

confidence: 99%

Pathophysiology of COVID-19: Why Children Fare Better than Adults?

et al. 2020

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“…Previous study showed that when peripheral monocytes derived from psoriasis patients were induced in vitro, the ratio of M1/M2 macrophage polarization was higher, compared with healthy control [9] . It indicates that monocytes in psoriasis might undergo a reprogramming process-trained immunity [7] , acquiring the preference to M1 polarization. Derived from monocytes, M0 macrophages in psoriatic plaque might also be reprogrammed in the same way.…”

Section: Discussionmentioning

confidence: 99%

“…These innate-derived IL-17 act as critical element in immune response to self antigens and sustaining in ammation, involving in psoriasis pathogenesis [6] . Moreover, upon activation, innate immune system could undergo epigenetic and metabolic reprogramming, leading to enhanced responsiveness to a second challenge [7] . This process is called 'trained immunity', in the nature of innate immune memory, which could contribute to detrimental outcomes in chronic in ammatory diseases [7] .…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, upon activation, innate immune system could undergo epigenetic and metabolic reprogramming, leading to enhanced responsiveness to a second challenge [7] . This process is called 'trained immunity', in the nature of innate immune memory, which could contribute to detrimental outcomes in chronic in ammatory diseases [7] . Therefore, further investigation of innate immune status in psoriatic plaque is important to understand the pathogenesis of psoriasis and improve the therapeutic e cacy.…”

Section: Introductionmentioning

confidence: 99%

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Profiles of Innate Immune Cell Infiltration and Related Core Genes in Psoriasis

Gong

Wang

2020

Preprint

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Background: Psoriasis is an inflammatory skin disease with substantial morbidity. Numerous patients with psoriasis experience recurrence after therapy. The underlying mechanism about psoriasis is still not fully understood. Some evidences suggest that innate immunity may play an unexpected and important role in active severe psoriasis. In this work, the deconvolution algorithm CIBERSORT was conducted to identify the infiltration of innate immune cells and related core genes in psoriatic plaque.Results: Datasets from the Gene Expression Omnibus, including 407 psoriasis lesional, 373 non-lesional and 91 normal skin samples, were downloaded for analysis. Considerable differences of the innate immune cell composition were uncovered between psoriatic plaque and control skin. Results revealed that γδ T cells, resting NK cells, M0 macrophages, M1 macrophages, activated dendritic cells and neutrophils were significantly increased in psoriatic skin, while resting mast cells and active NK cells were significantly decreased. Moreover, the proportion of M0 macrophages or resting mast cells was found to be associated with disease severity. Spearman correlation analysis suggests that RORC and S100A12 genes were related to disease severity, while genes including S100A12, CLEC4C, IL-19, AIM2, IL-17F, PPARGC1A, were correlated with biologics treatment response.Conclusions: Collectively, this work displays innate immune status in psoriatic skin, and provides novel clues for clinical decisions and mechanism study.

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“…Bacillus Calmette-Guerin (BCG) vaccination is also shown to be protective against SARS CoV-2 in a recent study, conducted in 131 countries (12), by determining ten times elevated mortality rate in countries, where BCG is not in routine vaccination program, compared to the countries, where BCG vaccination is applied (40 million vs 4.28 million). BCG vaccine and other live-attenuated vaccines are known to improve general innate immunity not only for the target disease but also for other infections (13). Another explanation for this, might be of these characteristics of live-attenuated vaccines is that those vaccines develop immune memory (14).…”

Section: Discussionmentioning

confidence: 99%

Do childhood measles and DTaP vaccination decrease the mortality rate caused by SARS CoV-2 in OECD countries?: An Epidemiologic Study

Güven

Şaşmaz

Eyüpoğlu

et al. 2020

Preprint

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Background The mortality rates caused by SARS CoV-2 differ between countries and this difference might be explained by several reasons. Childhood vaccination rate is thought to be one of them. Therefore, present study aimed to examine the possible relationship between DTaP (diphtheria, tetanus, acellular pertussis vaccine) and measles vaccination rates of Organization for Economic Co-operation and Development (OECD) countries and case fatality rate (CFR) caused by SARS CoV-2.Methods A total of 32 OECD countries, of northern hemisphere, have been included in this study. Statistical analysis performed according to the CFR data of these countries based on SARS CoV-2. The CFR data calculated according to the total mortality count of a specific country for the 3-month period down from the date when first SARS CoV-2 case was observed. Results Based on the correlation levels of vaccination rates of OECD countries with a period of 3-month CFR, a strong negative correlation of significance between CFR and measles (r=-0.479, p=0.006) were pointed, while a negative but not significant correlation were seen between CFR and DTaP vaccination rates (r=-264.0, p=0.145). Conclusion Depending on the results of the study, lower CFR based on COVID-19, is suggested to be related to the successful vaccination rates of those OECD countries. Therefore, further effort is required to improve rates of childhood vaccination not only for specified diseases, but either possible protection against COVID-19 worldwide. Trial Registration: This study is registered to clinicaltrials.gov with trial number: NCT04468802.

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Defining trained immunity and its role in health and disease

Cited by 1,514 publications

References 190 publications

Pathophysiology of COVID-19: Why Children Fare Better than Adults?

Pathophysiology of COVID-19: Why Children Fare Better than Adults?

Profiles of Innate Immune Cell Infiltration and Related Core Genes in Psoriasis

Do childhood measles and DTaP vaccination decrease the mortality rate caused by SARS CoV-2 in OECD countries?: An Epidemiologic Study

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