Highly multiplexed profiling of single-cell effector functions reveals deep functional heterogeneity in response to pathogenic ligands

Authors:

Abstract
Significance: We demonstrated codetection of 42 immune effector proteins in single cells, representing the highest multiplexing recorded to date for a single-cell secretion assay. Using this platform to profile differentiated macrophages stimulated with lipopolysaccharide reveals previously unobserved deep functional heterogeneity and varying levels of pathogenic activation, which is conserved throughout the cell activation process and prevails as it is extended to other Toll-like receptor (TLR) ligands and to primary human macrophages. The results indicate that the phenotypically similar cell population could still exhibit a large degree of intrinsic heterogeneity at the cell function level. This technology enables full-spectrum dissection of immune functional states in response to pathogenic stimulation and allows for more comprehensive and accurate monitoring of cellular immunity.
Funding Information
  • HHS | National Institutes of Health (U01CA164252)
  • HHS | NIH | National Cancer Institute (U54CA143798)
  • HHS | NIH | National Cancer Institute (R00CA136759)
  • National Science Foundation (MCB-1149728)
  • HHS | National Institutes of Health (R01CA164729)