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Innate Immune Memory: The Latest Frontier of Adjuvanticity.

Töpfer E, Boraschi D, Italiani P - J Immunol Res (2015)

Bottom Line: This effect has been most extensively investigated for the tuberculosis vaccine strain Bacillus Calmette-Guérin (BCG).Thus, vaccines are likely to nonspecifically affect the overall immunological status of individuals in a clinically relevant manner.As a consequence, future vaccine strategies ought to take into account the contribution of innate memory through appropriate design of formulations and administration scheduling.

View Article: PubMed Central - PubMed

Affiliation: Institute of Protein Biochemistry, National Research Council, 80131 Naples, Italy.

ABSTRACT
Recent findings in the field of immune memory have demonstrated that B and T cell mediated immunity following infections are enhanced by the so-called trained immunity. This effect has been most extensively investigated for the tuberculosis vaccine strain Bacillus Calmette-Guérin (BCG). Epidemiological studies suggest that this vaccine is associated with a substantial reduction in overall child mortality that cannot be solely explained by prevention of the target disease but that it seems to rely on inducing resistance to other infections. Upon infection or vaccination, monocytes/macrophages can be functionally reprogrammed so as to display an enhanced defensive response against unrelated infections. Epigenetic modifications seem to play a key role in the induction of this "innate memory." These findings are revolutionising our knowledge of the immune system, introducing the concept of memory also for mammalian innate immunity. Thus, vaccines are likely to nonspecifically affect the overall immunological status of individuals in a clinically relevant manner. As a consequence, future vaccine strategies ought to take into account the contribution of innate memory through appropriate design of formulations and administration scheduling.

No MeSH data available.


Related in: MedlinePlus

Main mechanisms involved in trained immune memory. In the picture the main mechanisms believed to underlie innate memory are shown. (a) Altered PRR expression. Phenotypic changes of innate immune cells with memory properties involve increased expression of PRRs on the cell surface and improved pathogen recognition. (b) Metabolic reprogramming. Innate immune memory requires a metabolic shift, which involves Warburg metabolism. The metabolism of glucose is shifted toward increased glycolysis with production of lactate and decreased oxidative phosphorylation. (c) Epigenetic reprogramming. Trimethylation of H3 at lysine 4 (H3K4me3) is a marker of promoter activation for proinflammatory genes specifically induced by β-glucan-dependent memory. (d) Altered cytokines release. Trained memory responses are characterised by an enhanced protective inflammatory reaction. The different patterns of cytokine release may be involved in the systemic establishment of a memory phenotype, reaching far/secluded anatomical sites (as suggested for brain responses and demonstrated in plants).
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fig1: Main mechanisms involved in trained immune memory. In the picture the main mechanisms believed to underlie innate memory are shown. (a) Altered PRR expression. Phenotypic changes of innate immune cells with memory properties involve increased expression of PRRs on the cell surface and improved pathogen recognition. (b) Metabolic reprogramming. Innate immune memory requires a metabolic shift, which involves Warburg metabolism. The metabolism of glucose is shifted toward increased glycolysis with production of lactate and decreased oxidative phosphorylation. (c) Epigenetic reprogramming. Trimethylation of H3 at lysine 4 (H3K4me3) is a marker of promoter activation for proinflammatory genes specifically induced by β-glucan-dependent memory. (d) Altered cytokines release. Trained memory responses are characterised by an enhanced protective inflammatory reaction. The different patterns of cytokine release may be involved in the systemic establishment of a memory phenotype, reaching far/secluded anatomical sites (as suggested for brain responses and demonstrated in plants).

Mentions: The main mechanisms of trained memory are summarised in Figure 1. Whether all these mechanisms are concomitantly involved or which one is mainly responsible for shifting innate immune cells toward a memory-like phenotype is still a matter of investigation.


Innate Immune Memory: The Latest Frontier of Adjuvanticity.

Töpfer E, Boraschi D, Italiani P - J Immunol Res (2015)

Main mechanisms involved in trained immune memory. In the picture the main mechanisms believed to underlie innate memory are shown. (a) Altered PRR expression. Phenotypic changes of innate immune cells with memory properties involve increased expression of PRRs on the cell surface and improved pathogen recognition. (b) Metabolic reprogramming. Innate immune memory requires a metabolic shift, which involves Warburg metabolism. The metabolism of glucose is shifted toward increased glycolysis with production of lactate and decreased oxidative phosphorylation. (c) Epigenetic reprogramming. Trimethylation of H3 at lysine 4 (H3K4me3) is a marker of promoter activation for proinflammatory genes specifically induced by β-glucan-dependent memory. (d) Altered cytokines release. Trained memory responses are characterised by an enhanced protective inflammatory reaction. The different patterns of cytokine release may be involved in the systemic establishment of a memory phenotype, reaching far/secluded anatomical sites (as suggested for brain responses and demonstrated in plants).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4561982&req=5

fig1: Main mechanisms involved in trained immune memory. In the picture the main mechanisms believed to underlie innate memory are shown. (a) Altered PRR expression. Phenotypic changes of innate immune cells with memory properties involve increased expression of PRRs on the cell surface and improved pathogen recognition. (b) Metabolic reprogramming. Innate immune memory requires a metabolic shift, which involves Warburg metabolism. The metabolism of glucose is shifted toward increased glycolysis with production of lactate and decreased oxidative phosphorylation. (c) Epigenetic reprogramming. Trimethylation of H3 at lysine 4 (H3K4me3) is a marker of promoter activation for proinflammatory genes specifically induced by β-glucan-dependent memory. (d) Altered cytokines release. Trained memory responses are characterised by an enhanced protective inflammatory reaction. The different patterns of cytokine release may be involved in the systemic establishment of a memory phenotype, reaching far/secluded anatomical sites (as suggested for brain responses and demonstrated in plants).
Mentions: The main mechanisms of trained memory are summarised in Figure 1. Whether all these mechanisms are concomitantly involved or which one is mainly responsible for shifting innate immune cells toward a memory-like phenotype is still a matter of investigation.

Bottom Line: This effect has been most extensively investigated for the tuberculosis vaccine strain Bacillus Calmette-Guérin (BCG).Thus, vaccines are likely to nonspecifically affect the overall immunological status of individuals in a clinically relevant manner.As a consequence, future vaccine strategies ought to take into account the contribution of innate memory through appropriate design of formulations and administration scheduling.

View Article: PubMed Central - PubMed

Affiliation: Institute of Protein Biochemistry, National Research Council, 80131 Naples, Italy.

ABSTRACT
Recent findings in the field of immune memory have demonstrated that B and T cell mediated immunity following infections are enhanced by the so-called trained immunity. This effect has been most extensively investigated for the tuberculosis vaccine strain Bacillus Calmette-Guérin (BCG). Epidemiological studies suggest that this vaccine is associated with a substantial reduction in overall child mortality that cannot be solely explained by prevention of the target disease but that it seems to rely on inducing resistance to other infections. Upon infection or vaccination, monocytes/macrophages can be functionally reprogrammed so as to display an enhanced defensive response against unrelated infections. Epigenetic modifications seem to play a key role in the induction of this "innate memory." These findings are revolutionising our knowledge of the immune system, introducing the concept of memory also for mammalian innate immunity. Thus, vaccines are likely to nonspecifically affect the overall immunological status of individuals in a clinically relevant manner. As a consequence, future vaccine strategies ought to take into account the contribution of innate memory through appropriate design of formulations and administration scheduling.

No MeSH data available.


Related in: MedlinePlus