Organotins differentially modulate immune reporter responses across THP-1 monocyte-macrophage states

Organotin compounds perturb immune function, but their effects are typically assessed in a single cellular context despite the plasticity of macrophages. We built a state-resolved platform comprising six separate THP-1 promoter-reporter lines spanning cytokine, chemokine and macrophage-marker programs, and exposed THP-1 monocytes and differently conditioned macrophage-like cells to eight structurally diverse organotins. Here, we show that both the direction and pattern of immune reporter responses to organotins depend on cellular state. The same exposure could reverse direction between states, and inflammatory reporters did not move in parallel. CXCL9 and CD80 responses were predominantly reduced, whereas CD163 responses varied with conditioning, with several exposures reversing direction between M2a-like and M2c-like states. Matched-concentration comparisons further revealed distinct response profiles across organotins. Together, these findings show that immune responses to organotins depend on both cellular state and compound identity. This state-resolved approach offers a framework for investigating the immune effects of other chemicals and for advancing mechanistic studies of organotin immunotoxicity.