Systems approaches combine what we already know (prior biological knowledge) with the analysis of massive amounts of new data (collected through global measurement technologies and computational methods). Merging these levels of information can reveal novel regulatory interactions between molecules and places them in context within the immune system. Identifying regulatory nodes in immune cells that control specific sub-networks of the innate response is critical to the development of therapeutic strategies that aim to either harness specific immune functions, such as for vaccine adjuvants, or to mitigate inflammation-driven diseases such as atherosclerosis and lupus. Two key cell types in the innate immune system are macrophages and dendritic cells, which display an arsenal of receptors for detecting pathogens and play critical roles in pathogen clearance, cytokine production, and the initiation of adaptive immunity. Systems biology studies of macrophages and dendritic cells in the Aderem Lab have generated testable hypotheses for the role of a large number of molecules in innate immune responses. We are testing how mutating these molecules or perturbing their networks will impact immune responses against tuberculosis, HIV, influenza, and other pathogens.