The integrated stress response in apicomplexan and trypanosomatid parasites: balancing survival and pathogenesis

Parasites rely on their hosts for survival and replication and therefore face major challenges as they transition between hosts and encounter hostile microenvironments. Over evolution, these organisms have developed complex mechanisms to rapidly adapt to environmental fluctuations and to exploit host cellular machinery for persistence and dissemination. Among the pathways parasites deploy to cope with stress is the Integrated Stress Response (ISR), a conserved mechanism present in both parasites and their hosts, yet built on partially distinct molecular components. This shared but divergent pathway constitutes a critical battleground that reflects host-parasite coevolution, where host-protective responses intersect with parasite adaptive strategies. This review summarizes the current understanding of how protozoan parasites engage their own ISR-like programs to adapt to harsh environments and how they modulate host ISR signaling to establish and maintain successful infections.