A systems immunology approach to investigate cytokine responses to viruses and bacteria and their association with disease.

Lijing Lin, John A Curtin, Eteri Regis, Aurica Hirsman, Rebecca Howard, Mauro Tutino, Michael R Edwards, Mattia Prosperi, Angela Simpson, Magnus Rattray, Adnan Custovic, Sebastian L Johnston

Scientific reports 2022 Aug 05

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Patterns of human immune responses to viruses and bacteria and how this impacts risk of infections or onset/exacerbation of chronic respiratory diseases are poorly understood. In a population-based birth cohort, we measured peripheral blood mononuclear cell responses (28 cytokines) to respiratory viruses and bacteria, Toll-like receptor ligands and phytohemagglutinin, in 307 children. Cytokine responses were highly variable with > 1000-fold differences between children. Machine learning revealed clear distinction between virus-associated and bacteria-associated stimuli. Cytokines clustered into three functional groups (anti-viral, pro-inflammatory and T-cell derived). To investigate mechanisms potentially explaining such variable responses, we investigated cytokine Quantitative Trait Loci (cQTLs) of IL-6 responses to bacteria and identified nine (eight novel) loci. Our integrative approach describing stimuli, cytokines and children as variables revealed robust immunologically and microbiologically plausible clustering, providing a framework for a greater understanding of host-responses to infection, including novel genetic associations with respiratory disease. © 2022. The Author(s).

Citation

Lijing Lin, John A Curtin, Eteri Regis, Aurica Hirsman, Rebecca Howard, Mauro Tutino, Michael R Edwards, Mattia Prosperi, Angela Simpson, Magnus Rattray, Adnan Custovic, Sebastian L Johnston. A systems immunology approach to investigate cytokine responses to viruses and bacteria and their association with disease. Scientific reports. 2022 Aug 05;12(1):13463