Modulation of macrophage responses by the vaccine adjuvant alum
Citation:
GORMAN, AOIFE LOUISE LOUISE, Modulation of macrophage responses by the vaccine adjuvant alum, Trinity College Dublin.School of Biochemistry & Immunology, 2020Download Item:
Abstract:
Recent findings have challenged the classical view of innate versus adaptive immunity, suggesting that innate cells can retain some memory of past immunological insults. This trained immunity which allows for primed cellular responses to secondary infections is independent of T and B cells and is mediated by innate cells such as monocytes and macrophages. While it has been shown that certain live vaccines such as BCG can induce trained immunity, the training effects of non-living vaccines incorporating the widely used vaccine adjuvant alum have not been addressed. Alum has been predominantly used in several childhood vaccines due to effectiveness in promoting antibody responses and robust safety profile. However, the immunomodulatory effects of alum have not been fully elucidated. Using the in vitro model of training, alum was found to train innate cells to adopt a distinct morphology in addition to an increased capacity to proliferate through enhanced metabolic activity. The transcriptional profile of alum-trained macrophages was explored using the NanoString Inflammation panel one week after training in vitro. Alum globally downregulated pro-inflammatory gene expression while a small group of upregulated genes was identified which may shed light on the mechanisms underlying the establishment of these unconventional anti-inflammatory macrophages. One such gene, Il1rn, that encodes IL-1Ra, the natural inhibitor of the pro-inflammatory cytokine IL1-β, was significantly increased in response to alum alone. Interestingly, secretion of this anti- inflammatory cytokine was hindered by pre-treatment with rapamycin. Furthermore, the metabolic profile of macrophages stimulated with alum was reversed by rapamycin. These data suggest that stimulating macrophages with alum may favour a pro-resolution phenotype via activation of mammalian target of rapamycin (mTOR), altering cellular metabolism and proliferative capacity.
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Irish Research Council (IRC)
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https://tcdlocalportal.tcd.ie/pls/EnterApex/f?p=800:71:0::::P71_USERNAME:GORMANAODescription:
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Author: GORMAN, AOIFE LOUISE LOUISE
Advisor:
Lavelle, EdwardPublisher:
Trinity College Dublin. School of Biochemistry & Immunology. Discipline of BiochemistryType of material:
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Full text availableKeywords:
Innate Training, Adjuvants, Macrophages, ImmunologyMetadata
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