Signature sets differentially upregulated only in childhood TB were notably replete of IFN regulated genes but enriched with other immune pathways including elevation of alternative antimicrobial defense mechanisms (H2AFJ, HISTIH2BG, and CTSG) and multi-functional IL27 that blocks IL-17 and IRF1 signaling as well as counter T-reg functions, platelet adhesion, and metabolic pathways involved in transport of glucose and other sugars, erythrocytes uptake of carbon dioxide and release of oxygen and cell surface interactions at the vascular wall. Here, CTSG is linked to tuberculosis.