This study aims to infer a contextualized protein-protein interaction (PPI) network in human macrophages, integrating various data sources to enhance the biological significance of the network. The authors used the Agile Protein Interaction DataAnalyzer (APIID) dataset and combined it with meta-data to create a macrophage-specific interactome. This interactome is enriched in experimentally verified interactions and proteins involved in macrophage-related biological processes, such as immune response activation and apoptosis regulation. A case study on Mycobacterium tuberculosis (MTB) infection highlights the cellular processes induced, emphasizing the importance of considering protein interactions rather than gene expression levels. The contextualized interactome is validated through functional enrichment analysis and comparisons with other interactomes, demonstrating its specificity and relevance in understanding host responses to MTB infection. The study underscores the value of contextualizing interactomes to improve the biological significance of bioinformatics analyses in infectious diseases research.This study aims to infer a contextualized protein-protein interaction (PPI) network in human macrophages, integrating various data sources to enhance the biological significance of the network. The authors used the Agile Protein Interaction DataAnalyzer (APIID) dataset and combined it with meta-data to create a macrophage-specific interactome. This interactome is enriched in experimentally verified interactions and proteins involved in macrophage-related biological processes, such as immune response activation and apoptosis regulation. A case study on Mycobacterium tuberculosis (MTB) infection highlights the cellular processes induced, emphasizing the importance of considering protein interactions rather than gene expression levels. The contextualized interactome is validated through functional enrichment analysis and comparisons with other interactomes, demonstrating its specificity and relevance in understanding host responses to MTB infection. The study underscores the value of contextualizing interactomes to improve the biological significance of bioinformatics analyses in infectious diseases research.