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Early IFNβ secretion determines variable downstream IL-12p70 responses upon TLR4 activation

Abstract : The interleukine-12 (IL-12) family comprises the only heterodimeric cytokines mediating diverse functional effects. We previously reported a striking bi-modal IL-12p70 response to LPS stimulation in healthy donors. Herein, we demonstrate that IFNβ isa major upstream determinant of IL-12p70 production, which is also associated with numbers and activation of circulatingmonocytes. Integrative modelling of proteomic, genetic, epigenomic and cellular data confirmsIFNβ as key forLPS induced IL-12p70, and allowed us to compare the relative effects of each of these parameters on variable cytokine responses.Clinical relevance of ourfindings is supportedby reduced IFNβ-IL-12p70 responses in patients hospitalized with acute SARS-CoV-2infection,or chronically infected with hepatitis C (HCV).Importantly these responses are resolved after viral clearance. Our systems immunology approach definesa better understanding of IL-12p70 and IFNβ in healthy and infected persons, providing insights into howcommon genetic and epigenetic variation may impact immune responses to bacterial infection.
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Submitted on : Tuesday, June 1, 2021 - 11:06:20 AM
Last modification on : Monday, June 20, 2022 - 9:50:06 AM
Long-term archiving on: : Thursday, September 2, 2021 - 6:30:04 PM

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Celine Posseme, Alba Llibre, Bruno Charbit, Vincent Bondet, Vincent Rouilly, et al.. Early IFNβ secretion determines variable downstream IL-12p70 responses upon TLR4 activation. Cell Reports, Elsevier Inc, 2022, ⟨10.1016/j.celrep.2022.110989⟩. ⟨pasteur-03244390⟩

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