Adjuvant effects of multifunctional transcription factor and BCG target YB-1: exogenous YB-1 enhances specific antibody production<i>in vivo</i>and protects mice against lethal<i>E. coli</i>challenge

Shepelyakovskaya, A. O.; Alekseeva, Ludmila; Meshcheryakova, E. N.; Boziev, Khanafiy; Tsitrina, Alexandra; Иванов, В. Т.; Бровко, Ф. А.; Kotelevtsev, Yuri; Lathe, Richard; Ламан, А. Г.

doi:10.1101/2022.11.09.515841

Cited by 3 publications

(1 citation statement)

References 65 publications

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“…Blood levels of YB-1 are remarkably elevated in patients with sepsis [ 130 ], suggesting that YB-1 upregulation may be a protective response to infection. Indeed, treatment of mice with recombinant YB-1 protein was reported to act as an adjuvant to increase the immune response to an unrelated antigen ( Yersinia pestis V antigen) and significantly promoted survival against lethal bacterial infection ( Escherichia coli ) [ 131 ], although this requires confirmation, and is active in a mouse model of AD [ 132 ].…”

Section: Mycobacteria Induce Trained Innate Immunity But Some Effects...mentioning

confidence: 99%

Vaccines and Dementia: Part I. Non-Specific Immune Boosting with BCG: History, Ligands, and Receptors

Greenblatt,

Lathe

2024

JAD

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Vaccines such as Bacille Calmette–Guérin (BCG) can apparently defer dementia onset with an efficacy better than all drugs known to date, as initially reported by Gofrit et al. (PLoS One 14, e0224433), now confirmed by other studies. Understanding how and why is of immense importance because it could represent a sea-change in how we manage patients with mild cognitive impairment through to dementia. Given that infection and/or inflammation are likely to contribute to the development of dementias such as Alzheimer’s disease (Part II of this work), we provide a historical and molecular background to how vaccines, adjuvants, and their component molecules can elicit broad-spectrum protective effects against diverse agents. We review early studies in which poxvirus, herpes virus, and tuberculosis (TB) infections afford cross-protection against unrelated pathogens, a concept known as ‘trained immunity’. We then focus on the attenuated TB vaccine, BCG, that was introduced to protect against the causative agent of TB, Mycobacterium tuberculosis. We trace the development of BCG in the 1920 s through to the discovery, by Freund and McDermott in the 1940 s, that extracts of mycobacteria can themselves exert potent immunostimulating (adjuvant) activity; Freund’s complete adjuvant based on mycobacteria remains the most potent immunopotentiator reported to date. We then discuss whether the beneficial effects of BCG require long-term persistence of live bacteria, before focusing on the specific mycobacterial molecules, notably muramyl dipeptides, that mediate immunopotentiation, as well as the receptors involved. Part II addresses evidence that immunopotentiation by BCG and other vaccines can protect against dementia development.

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Section: Mycobacteria Induce Trained Innate Immunity But Some Effects...mentioning

confidence: 99%

Vaccines and Dementia: Part I. Non-Specific Immune Boosting with BCG: History, Ligands, and Receptors

Greenblatt,

Lathe

2024

JAD

Self Cite

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Extracellular Cold Shock Protein YB-1 Induces Tolerance to GMDP and LPS in Mouse Macrophage Cell Line J774

Alekseeva,

Laman,

Meshcherykova

et al. 2023

Russ J Bioorg Chem

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Extracellular Cold Shock Protein YB-1 Induces Tolerance to GMDP and LPS in Mouse Macrophage Cell Line J774

Alekseeva,

Laman,

Meshcherykova

et al. 2023

RUBI

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Cold shock protein YB-1 is involved in the regulation of a huge number of fundamental biological processes. Previously, we showed that YB-1 is also involved in the process of recognition of muramylpeptide GMDP by the innate immune receptor NOD2 and is able upon preliminary administration to protect mice from death in a model of septic shock induced by Escherichia coli bacteria. We hypothesized that its protective effect may be associated with the development of a state of tolerance (“nonresponsiveness”). Changes in the cellular response were assessed by the level of mRNA expression of the target molecules by quantitative PCR analysis combined with reverse transcription. We tested the possibility of tolerance induction by the YB-1 protein in a model system on the J774 mouse macrophage cell line with the participation of E. coli bacterial cell wall components, immunostimulants GMDP (NOD2 receptor agonist) and LPS (TLR4 receptor agonist). Pretreatment of cells with YB-1 resulted in a significant decrease in the level of mRNA expression of pro-inflammatory cytokines IL-1β, TNF-α, and IL-6 in response to further stimulation with GMDP and LPS, as well as significant changes in the expression of mRNA of RIP2 and MyD88 adapter molecules and components of transcriptional factor NF-κB. Our data show that YB-1 is able to induce tolerance to such as GMDP and LPS immunostimulants, apparently by increasing the production of the anti-inflammatory cytokine IL-1Ra and the SOCS1 inhibitor. A more precise characterization of the features of the YB-1-induced tolerogenic immune response requires further research.

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Adjuvant effects of multifunctional transcription factor and BCG target YB-1: exogenous YB-1 enhances specific antibody productionin vivoand protects mice against lethalE. colichallenge

Cited by 3 publications

References 65 publications

Vaccines and Dementia: Part I. Non-Specific Immune Boosting with BCG: History, Ligands, and Receptors

Vaccines and Dementia: Part I. Non-Specific Immune Boosting with BCG: History, Ligands, and Receptors

Extracellular Cold Shock Protein YB-1 Induces Tolerance to GMDP and LPS in Mouse Macrophage Cell Line J774

Extracellular Cold Shock Protein YB-1 Induces Tolerance to GMDP and LPS in Mouse Macrophage Cell Line J774

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