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    Hyper-Inflammatory Monocyte Activation Following Endotoxin Exposure in Food Allergic Infants

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    Author
    Neeland, MR; Novakovic, B; Dang, TD; Perrett, KP; Koplin, JJ; Saffery, R
    Date
    2020-09-24
    Source Title
    Frontiers in Immunology
    Publisher
    FRONTIERS MEDIA SA
    University of Melbourne Author/s
    Koplin, Jennifer; Saffery, Richard; Perrett, Kirsten; Dang, Thanh; Neeland, Melanie; Novakovic, Boris
    Affiliation
    Paediatrics (RCH)
    Melbourne School of Population and Global Health
    Metadata
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    Document Type
    Journal Article
    Citations
    Neeland, M. R., Novakovic, B., Dang, T. D., Perrett, K. P., Koplin, J. J. & Saffery, R. (2020). Hyper-Inflammatory Monocyte Activation Following Endotoxin Exposure in Food Allergic Infants. FRONTIERS IN IMMUNOLOGY, 11, https://doi.org/10.3389/fimmu.2020.567981.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/251735
    DOI
    10.3389/fimmu.2020.567981
    Abstract
    Several recent studies have reported a key role for innate cell hyper-responsiveness in food allergy. This has predominantly been observed in early life, with evidence that innate immune function may return to baseline if food allergy resolves in later childhood. Hallmarks of hyper-responsiveness include increased circulating frequency of monocytes and altered innate cell cytokine responses to in vitro exposure with bacterial endotoxin. These features mirror the defining signatures of trained innate immunity, seen in other complex diseases. In this study, detailed immune cell and cytokine profiling was performed on peripheral blood mononuclear cells at baseline from 27 1 year old infants in the HealthNuts cohort (n = 16 egg allergic and n = 11 non-allergic healthy controls) and following monocyte stimulation. We show that egg allergic infants have increased frequency of circulating monocytes, reduced numbers of regulatory CD4 T cells and increased monocyte: CD4 T cell ratios relative to healthy controls. Monocytes from both egg allergic and non-allergic infants responded to endotoxin stimulation with rapid cytokine production and downregulation of the surface receptor CD16, however monocytes from egg allergic infants were hyper-responsive, producing significantly more inflammatory cytokines (TNFα, IL-6, IL-1β, IL-8) and innate cell recruiting factors (MIP-1α) than healthy controls. This work indicates that monocytes of food allergic infants are programmed to a hyper-inflammatory phenotype and that the development of food allergy may be associated with trained immunity in early life.

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