Social Network Architecture of Human Immune Cells Unveiled by Quantitative Proteomics
J. Rieckmann1, R. Geiger2,3, D. Hornburg1, K. Kveler4 ,T. Wolf2,3, D. Jarrossay2,3,
S. S. Shen-Orr4, A. Lanzavecchia2,3, M. Mann1, F. Meissner1
1Max Planck Institute of Biochemistry, Martinsried, Bayern, Germany
2Institute for Research in Biomedicine, Bellinzona, Ticino, Switzerland
3Institute of Microbiology, Zürich, Zürich, Switzerland
4Technion Institute of Technology, Haifa, Israel
The immune system is unique in its dynamic interplay between numerous cell types. However, a system-wide view of how immune cells communicate to protect against disease has not been established. Here, we applied high-resolution mass spectrometry-based proteomics to characterize 28 primary human hematopoietic cell populations in steady and activated states at a depth of > 10,000 proteins. Cell-type-specific protein copy numbers reveal that immune cells are most specialized at the level of ligands and receptors, thereby connecting distinct functions of the immune system. By integrating total and secreted proteomes, we deduce paracrine immune dynamics upon microbial encounter and discover fundamental intercellular communication structures as well as novel connections between cellular senders and receivers of biological information. Our comprehensive cell-type-resolved proteomic resource of human immune cells provides a framework for the orchestration of cellular interplay and a reference for altered communication associated with pathology.