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Published in Cell reports - 28 Jun 2022

Posseme C, Llibre A, Charbit B, Bondet V, Rouilly V, Saint-André V, Boussier J, Bergstedt J, Smith N, Townsend L, Sugrue JA, Ní Cheallaigh C, Conlon N, Rotival M, Kobor MS, Mottez E, Pol S, Patin E, Albert ML, Quintana-Murci L, Duffy D, ,

Link to Pubmed [PMID] – 35767946

Link to DOI – 10.1016/j.celrep.2022.110989

Cell Rep 2022 Jun; 39(13): 110989

The interleukin-12 (IL-12) family comprises the only heterodimeric cytokines mediating diverse functional effects. We previously reported a striking bimodal IL-12p70 response to lipopolysaccharide (LPS) stimulation in healthy donors. Herein, we demonstrate that interferon β (IFNβ) is a major upstream determinant of IL-12p70 production, which is also associated with numbers and activation of circulating monocytes. Integrative modeling of proteomic, genetic, epigenomic, and cellular data confirms IFNβ as key for LPS-induced IL-12p70 and allowed us to compare the relative effects of each of these parameters on variable cytokine responses. Clinical relevance of our findings is supported by reduced IFNβ-IL-12p70 responses in patients hospitalized with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or chronically infected with hepatitis C (HCV). Importantly, these responses are resolved after viral clearance. Our systems immunology approach defines a better understanding of IL-12p70 and IFNβ in healthy and infected persons, providing insights into how common genetic and epigenetic variation may impact immune responses to bacterial infection.

https://pubmed.ncbi.nlm.nih.gov/35767946