Trained immunity and host‐pathogen interactions

Peignier, Adeline; Parker, Dane

doi:10.1111/cmi.13261

Cited by 22 publications

(25 citation statements)

References 96 publications

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“…In addition to the adaptive immune response, there are some data suggesting that trained innate immunity might also have a role in protection against COVID-19. 88,89 Multiple clinical trials (eg, NCT04327206, NCT04328441, NCT04414267, and NCT04417335) are examining whether unrelated vac cines, such as the measles, mumps, and rubella vaccine and the Bacillus Calmette-Guérin vaccine, can elicit trained innate immunity and confer protection against COVID-19. It is crucial that research focuses on understanding the genetic drivers of infection and vaccineinduced humoral and cellular immunity to SARS-CoV-2, defining detailed targets of humoral and cellular immune responses at the epitope level, characterising the B-cell receptor and T-cell receptor repertoire elicited by infection or vaccination, and establishing the long-term durability, and maintenance, of protective immunity after infection or vaccination.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 immunity: review and applications to phase 3 vaccine candidates

2020

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Understanding immune responses to severe acute respiratory syndrome coronavirus 2 is crucial to understanding disease pathogenesis and the usefulness of bridge therapies, such as hyperimmune globulin and convalescent human plasma, and to developing vaccines, antivirals, and monoclonal antibodies. A mere 11 months ago, the canvas we call COVID-19 was blank. Scientists around the world have worked collaboratively to fill in this blank canvas. In this Review, we discuss what is currently known about human humoral and cellular immune responses to severe acute respiratory syndrome coronavirus 2 and relate this knowledge to the COVID-19 vaccines currently in phase 3 clinical trials.

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 immunity: review and applications to phase 3 vaccine candidates

2020

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“…MBL2 encodes a mannose-binding protein C that binds to mannose, activating the lectin complement pathway; TMPRSS2 cleaves the spike protein and ensures viral internalization [ 35 ], while the CD27 receptor is required for the generation and long-term maintenance of T-cell immunity. There are some data suggesting that trained innate immunity might also have a role in the protection against COVID-19 [ 36 , 37 ]. Several clinical trials are investigating whether unrelated vaccines, such as the measles, mumps, rubella vaccine, and the BCG vaccine can provoke trained innate immunity and improve protection against COVID-19 [ 38 ].…”

Section: Immune Response To Sars-cov-2mentioning

confidence: 99%

Immune Evasion of SARS-CoV-2 Emerging Variants: What Have We Learnt So Far?

Lazarević

Pravica

Miljanovic

et al. 2021

Viruses

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150

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Despite the slow evolutionary rate of SARS-CoV-2 relative to other RNA viruses, its massive and rapid transmission during the COVID-19 pandemic has enabled it to acquire significant genetic diversity since it first entered the human population. This led to the emergence of numerous variants, some of them recently being labeled “variants of concern” (VOC), due to their potential impact on transmission, morbidity/mortality, and the evasion of neutralization by antibodies elicited by infection, vaccination, or therapeutic application. The potential to evade neutralization is the result of diversity of the target epitopes generated by the accumulation of mutations in the spike protein. While three globally recognized VOCs (Alpha or B.1.1.7, Beta or B.1.351, and Gamma or P.1) remain sensitive to neutralization albeit at reduced levels by the sera of convalescent individuals and recipients of several anti-COVID19 vaccines, the effect of spike variability is much more evident on the neutralization capacity of monoclonal antibodies. The newly recognized VOC Delta or lineage B.1.617.2, as well as locally accepted VOCs (Epsilon or B.1.427/29-US and B1.1.7 with the E484K-UK) are indicating the necessity of close monitoring of new variants on a global level. The VOCs characteristics, their mutational patterns, and the role mutations play in immune evasion are summarized in this review.

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“…β-glucan can induce a long-term reprogramming in monocytes and macrophages, resulting in an enhanced pro-inflammatory function [ 2 ]. Integration of the transcriptome and metabolome of β-glucan-trained monocytes and macrophages revealed an upregulation of several major metabolic pathways, such as glucose metabolism, glutaminolysis, and the GSH synthesis pathway [ 8 , 9 ].…”

Section: Resultsmentioning

confidence: 99%

“…Trained immunity, the non-specific memory of the innate immune system, has been reported in plants, invertebrates, and mammals [ 1 ]. Innate immune cells challenged in vitro with microbial components such as β-glucan of the Candida albicans ( C. albicans ) cell wall or the Bacillus Calmette-Guérin (BCG) vaccine and restimulated with the same or different microbial insult a week after training, resulting in an increased capacity to produce cytokines in the trained cells compared with the non-trained cells [ 2 ]. Additionally, when mice were trained in vivo with β-glucan, BCG, or a low-dose of C. albicans , they showed lower mortality after lethal C. albicans reinfections [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Glutathione synthesis primes monocytes metabolic and epigenetic pathway for β-glucan-trained immunity

Huang

Weng

et al. 2021

Redox Biology

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Trained monocytes and macrophages produce reactive oxygen species (ROS), which trigger antioxidative glutathione (GSH) response to buffer the rising ROS. However, whether and how the trained immunity is shaped by GSH synthesis remains unknown. Here, we report that β-glucan-trained macrophages from mice harboring a myeloid-specific deletion of the catalytic subunit of glutamate-cysteine ligase ( Gclc) showed impaired GSH synthesis and decreased proinflammatory cytokine production in response to lipopolysaccharide challenge. Gclc deficiency compromised the activation of mammalian target of rapamycin-1 (mTOR) and expression of c-Myc transcription factors, abrogating the energy utilization and the metabolic reprogramming that allows β-glucan-trained macrophages to switch to glycolysis and glutaminolysis. Furthermore, Gclc deletion repressed effective H3K27me3 demethylation in the promoters of immunometabolic genes, such as Gls , Hk2, and Glut1, in β-glucan-trained macrophages by promoting the methyltransferase enhancer of zeste homolog 2 (EZH2). In vivo , myeloid-specific ablation of Gclc decreased the secretion of proinflammatory cytokines upon rechallenge with Candida albicans and these animals were less protected against the infection, compared with control littermates. Moreover, pharmacological inhibition of EZH2 enhanced the trained immunity response against Candida infection in Gclc-deficient mouse and human peripheral blood mononuclear cells treated with GCLC inhibitor buthionine sulfoximine (BSO). Thus, antioxidative GSH synthesis supports an environment conducive to β-glucan-induced metabolic and epigenetic reprogramming in trained immunity, allowing exploration of its functional consequences in autoimmune or inflammatory disease.

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Trained immunity and host‐pathogen interactions

Cited by 22 publications

References 96 publications

SARS-CoV-2 immunity: review and applications to phase 3 vaccine candidates

SARS-CoV-2 immunity: review and applications to phase 3 vaccine candidates

Immune Evasion of SARS-CoV-2 Emerging Variants: What Have We Learnt So Far?

Glutathione synthesis primes monocytes metabolic and epigenetic pathway for β-glucan-trained immunity

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