<i>Mycobacterium bovis </i><scp>BCG</scp> killed by extended freeze‐drying induces an immunoregulatory profile and protects against atherosclerosis

Ovchinnikova, Olga; Berge, Natacha; Kang, Chang–Yuil; Urien, Céline; Ketelhuth, Daniel F.J.; Pottier, J.; Drouet, Ludovic; Hansson, Göran K.; Marchal, G; Bäck, Magnus; Schwartz-Cornil, Isabelle; Lagranderie, M.

doi:10.1111/joim.12127

Cited by 35 publications

(31 citation statements)

References 34 publications

(47 reference statements)

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“…When injected to the mice, the peptide was shown to induce molecular and phenotypic changes in pDCs inducing tolerogenic properties associated with plaque degradation, diminished IFN-γ production and proliferation of T cells, activation of IL-10 secretion, and generation of Treg cells (Bocksch et al, 2007). Similar anti-atherosclerotic effects were reached with pDCs induced with Ep1.B and BCG EFD including induction of IL-10-producing Tregs (Ovchinnikova et al, 2014). Tolerogenic pDCs are likely to drive development of inducible Tregs in draining lymph nodes followed with expansion of Tregs but not tolerogenic pDCs in spleen.…”

Section: Tolerogenic and Immunosuppressive Properties Of Pdcs In Athementioning

confidence: 66%

“…Interestingly, atheroprotective tolerogenic pDCs could be induced by self-peptides such as an ApoE-derived peptide Ep1.B (Bellemore et al, 2014) or with bacterial antigens such as Mycobacterium bovis BCG (a causative agent of tuberculosis) killed by extended freeze-drying (BCG EFD) (Ovchinnikova et al, 2014). The ApoE peptide Ep1.B corresponds to C-terminal amino acids 239-252 of the human ApoE molecule and is atheroperotective itself (Stephens et al, 2008).…”

Section: Tolerogenic and Immunosuppressive Properties Of Pdcs In Athementioning

confidence: 99%

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Plasmacytoid dendritic cells: development, functions, and role in atherosclerotic inflammation

et al. 2014

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Plasmacytoid dendritic cells (pDCs) are a specialized subset of DCs that links innate and adaptive immunity. They sense viral and bacterial pathogens and release high levels of Type I interferons (IFN-I) in response to infection. pDCs were shown to contribute to inflammatory responses in the steady state and in pathology. In atherosclerosis, pDCs are involved in priming vascular inflammation and atherogenesis through production of IFN-I and chemokines that attract inflammatory cells to inflamed sites. pDCs also contribute to the proinflammatory activation of effector T cells, cytotoxic T cells, and conventional DCs. However, tolerogenic populations of pDCs are found that suppress atherosclerosis-associated inflammation through down-regulation of function and proliferation of proinflammatory T cell subsets and induction of regulatory T cells with potent immunomodulatory properties. Notably, atheroprotective tolerogenic DCs could be induced by certain self-antigens or bacterial antigens that suggests for great therapeutic potential of these DCs for development of DC-based anti-atherogenic vaccines.

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Section: Tolerogenic and Immunosuppressive Properties Of Pdcs In Athementioning

confidence: 66%

Section: Tolerogenic and Immunosuppressive Properties Of Pdcs In Athementioning

confidence: 99%

Plasmacytoid dendritic cells: development, functions, and role in atherosclerotic inflammation

et al. 2014

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“…In line with this, a recent genome-wide H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) analysis showed that the gene encoding receptor of oxLDL which is a marker of atherosclerosis, as well as genes directly related to inflammation, are enriched with H3K27ac in monocytes upon BCG vaccination (22), indicating that these pro-atherogenic genes are primed for an activation state in BCG-trained monocytes which could in turn contribute to atherosclerosis. However, it is noteworthy that several additional studies showed opposite results, pointing toward a beneficial effect of BCG vaccination on ASCVD (56)(57)(58). For example, in a human epidemiological cohort study, children vaccinated with BCG only showed a hazard ratio of 0.36 to develop cardiovascular diseases (58).…”

Section: Bcg-induced Training Programmentioning

confidence: 99%

Trained Immunity: An Underlying Driver of Inflammatory Atherosclerosis

et al. 2020

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Atherosclerosis, a chronic inflammatory disease of the arterial wall, is among the leading causes of morbidity and mortality worldwide. The persistence of low-grade vascular inflammation has been considered to fuel the development of atherosclerosis. However, fundamental mechanistic understanding of the establishment of non-resolving low-grade inflammation is lacking, and a large number of atherosclerosis-related cardiovascular complications cannot be prevented by current therapeutic regimens. Trained immunity is an emerging new concept describing a prolonged hyperactivation of the innate immune system after exposure to certain stimuli, leading to an augmented immune response to a secondary stimulus. While it exerts beneficial effects for host defense against invading pathogens, uncontrolled persistent innate immune activation causes chronic inflammatory diseases. In light of the above, the long-term over-activation of the innate immune system conferred by trained immunity has been recently hypothesized to serve as a link between non-resolving vascular inflammation and atherosclerosis. Here, we provide an overview of current knowledge on trained immunity triggered by various exogenous and endogenous inducers, with particular emphasis on its pro-atherogenic effects and the underlying intracellular mechanisms that act at both the cellular level and systems level. We also discuss how trained immunity could be mechanistically linked to atherosclerosis from both preclinical and clinical perspectives. This review details the mechanisms underlying the induction of trained immunity by different stimuli, and highlights that the intracellular training programs can be different, though partly overlapping, depending on the stimulus and the biological system. Thus, clinical investigation of risk factor specific innate immune memory is necessary for future use of trained immunity-based therapy in atherosclerosis.

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“…This notion was confirmed by the reduced atherosclerosis burden observed after adoptive transfer of such CD4 − CD25 + Tregs in mice and the increase in atherosclerosis by targeting the Treg‐specific forkhead box transcription factor FOXP3 . Furthermore, different immunization protocols, such as the inactivated tuberculosis vaccine, induce immunomodulation characterized by Treg expansion and have been associated with atheroprotection in mice . Treg elimination, however, also delays clearance of cholesterol‐rich lipoproteins and elevates plasma cholesterol concentrations by direct effects on hepatocytes , indicating that T lymphocyte regulation of atherosclerosis may exceed local immune circuits within the plaque.…”

Section: Cellular Components Of Plaque Inflammationmentioning

confidence: 92%

Regulation of atherosclerotic plaque inflammation

2015

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The immune reactions that regulate atherosclerotic plaque inflammation involve chemokines, lipid mediators and costimulatory molecules. Chemokines are a family of chemotactic cytokines that mediate immune cell recruitment and control cell homeostasis and activation of different immune cell types and subsets. Chemokine production and activation of chemokine receptors form a positive feedback mechanism to recruit monocytes, neutrophils and lymphocytes into the atherosclerotic plaque. In addition, chemokine signalling affects immune cell mobilization from the bone marrow. Targeting several of the chemokines and/or chemokine receptors reduces experimental atherosclerosis, whereas specific chemokine pathways appear to be involved in plaque regression. Leukotrienes are lipid mediators that are formed locally in atherosclerotic lesions from arachidonic acid. Leukotrienes mediate immune cell recruitment and activation within the plaque as well as smooth muscle cell proliferation and endothelial dysfunction. Antileukotrienes decrease experimental atherosclerosis, and recent observational data suggest beneficial clinical effects of leukotriene receptor antagonism in cardiovascular disease prevention. By contrast, other lipid mediators, such as lipoxins and metabolites of omega-3 fatty acids, have been associated with the resolution of inflammation. Costimulatory molecules play a central role in finetuning immunological reactions and mediate crosstalk between innate and adaptive immunity in atherosclerosis. Targeting these interactions is a promising approach for the treatment of atherosclerosis, but immunological side effects are still a concern. In summary, targeting chemokines, leukotriene receptors and costimulatory molecules could represent potential therapeutic strategies to control atherosclerotic plaque inflammation.

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Mycobacterium bovis BCG killed by extended freeze‐drying induces an immunoregulatory profile and protects against atherosclerosis

Cited by 35 publications

References 34 publications

Plasmacytoid dendritic cells: development, functions, and role in atherosclerotic inflammation

Plasmacytoid dendritic cells: development, functions, and role in atherosclerotic inflammation

Trained Immunity: An Underlying Driver of Inflammatory Atherosclerosis

Regulation of atherosclerotic plaque inflammation

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