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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number13463
JournalScientific Reports
Volume12
Issue number1
DOIs
Publication statusPublished - Dec 2022

Fingerprint

Dive into the research topics of 'A systems immunology approach to investigate cytokine responses to viruses and bacteria and their association with disease'. Together they form a unique fingerprint.

Cite this