Honey bee workers show very flexible aging patterns. Their typical behavioral progression, from nurse bees to forager bees, is associated with an onset of aging symptoms. Here, we studied how immune-activation can affect nurse and forager bees differently. Nurse and forager bees of identical chronological age were injected with vehicle control or the bacterial cell wall components lipopolysaccharide (LPS) or peptidoglycan (PGN). Next, we monitored survival and tested the expression of three immune-related genes. We confirm that forager bees die sooner than same-aged nurse bees, independent of the type of immune challenge. The relative gene expression patterns of two immune-related genes differed between the nurse and forager honey bees as well as between the treatment groups. Our findings support that nurse and forager honey bees can respond differently to immune challenge, despite a lack of detectable differences in mortality between treatments. This response was specifically associated with the workers’ behavioral caste, as the chronological age was similar among all tested animals.