Stress granules and cell death: crosstalk and potential therapeutic strategies in infectious diseases.

Pathogens exploit cellular stress responses to drive infection and evade immune responses, posing a persistent global health threat. Stress granules (SGs), dynamic mRNA hubs formed under stress, and regulated cell death (RCD) pathways collectively orchestrate host-pathogen dynamics. While SGs regulate mRNA translation to aid adaptation, RCD mechanisms-including apoptosis, pyroptosis, and necroptosis-eliminate infected cells to curb pathogen spread. However, pathogens subvert these systems through immune evasion strategies, such as disrupting SGs assembly or hijacking cell death signaling, to enhance replication and persistence. This review integrates molecular insights into SGs biogenesis and RCD regulation, dissecting their bidirectional interplay during infection. We highlight pathogen-specific tactics, such as viral proteases cleaving G3BP1 or bacterial effectors halting translation, to manipulate SGs dynamics and cell death pathways. Furthermore, we explore therapeutic opportunities targeting SGs assembly (e.g., eIF2α phosphorylation modulators, G3BP1 inhibitors) and RCD modulation (e.g., PANoptosis suppression, ferroptosis inducers) to restore host defense and mitigate immunopathology. By bridging molecular mechanisms with clinical applications, this analysis charts a course toward precision therapies leveraging the SGs-RCD axis to combat infectious diseases.