Mapping Pulmonary and Systemic Inflammation in Preschool Aged Children With Cystic Fibrosis

• Published in: Frontiers in immunology Vol. 12; p. 733217
• Main Authors: Shanthikumar, Shivanthan, Ranganathan, Sarath C, Saffery, Richard, Neeland, Melanie R
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 15.10.2021
• Subjects: BAL; Biomarkers - blood; Bronchoalveolar Lavage Fluid - immunology; Case-Control Studies; cystic fibrosis; Cystic Fibrosis - diagnosis; Cystic Fibrosis - immunology; Cystic Fibrosis - metabolism; Cytokines - blood; Flow Cytometry; Humans; immune profiling; Immunology; Immunophenotyping; Inflammation - diagnosis; Inflammation - immunology; Inflammation - metabolism; Inflammation Mediators - blood; Leukocytes - immunology; Leukocytes - metabolism; lung diseases; paediatrics; Phenotype; Pneumonia - diagnosis; Pneumonia - immunology; Pneumonia - metabolism; paediatrics; lung diseases; cystic fibrosis; immune profiling; flow cytometry; respiratory; BAL
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.733217

The immune landscape of the paediatric respiratory system remains largely uncharacterised and as a result, the mechanisms of globally important childhood respiratory diseases remain poorly understood. In this work, we used high parameter flow cytometry and inflammatory cytokine profiling to map the local [bronchoalveolar lavage (BAL)] and systemic (whole blood) immune response in preschool aged children with cystic fibrosis (CF) and aged-matched healthy controls. We demonstrate that children with CF show pulmonary infiltration of CD66b granulocytes and increased levels of MIP-1α, MIG, MCP-1, IL-8, and IL-6 in BAL relative to healthy control children. Proportions of systemic neutrophils positively correlated with age in children with CF, whilst systemic CD4 T cells and B cells were inversely associated with age. Inflammatory cells in the BAL from both CF and healthy children expressed higher levels of activation and migration markers relative to their systemic counterparts. This work highlights the utility of multiplex immune profiling and advanced analytical pipelines to understand mechanisms of lung disease in childhood.