Systems immunology integrates cutting-edge technologies with bioinformatics to comprehensively interrogate the immune response to infection at an organismal level. Here, we review studies that have leveraged transcriptomic, genomic, proteomic, and metabolomic approaches towards the identification of cells, molecules, and pathways implicated in host-pathogen interactions. We discuss the potential of single cell technologies for the study of human immune responses and, in this context, we advocate that systems immunology provides a conceptual and methodological framework to harness these approaches to address longstanding questions of fundamental and applied immunology. Recognizing that the field is still in its infancy, we also discuss current limitations of systems immunology, as well as the need for validation of key findings for the discipline to fulfill its promise.
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