Interplays between host pattern-recognition receptors and pathogen ligands in immunogenic cell death

The strategic induction of cell death serves as a crucial immune defense mechanism for the eradication of pathogen infections within host cells. Investigating the molecular mechanisms underlying immunogenic cell pathways has significantly enhanced our understanding of the host’s immunity. This review provides a comprehensive overview of the immunogenic cell death mechanisms triggered by pathogen infections, focusing on the critical role of pattern recognition receptors. In response to infections, host cells dictate a variety of cell death pathways, including apoptosis, pyroptosis, necrosis, and lysosomal cell death, which are essential for amplifying immune responses and controlling pathogen dissemination. Key components of these mechanisms are host cellular receptors that recognize pathogen-associated ligands. These receptors activate downstream signaling cascades, leading to the expression of immunoregulatory genes and the production of antimicrobial cytokines and chemokines. Particularly, the inflammasome, a multi-protein complex, plays a pivotal role in these responses by processing pro-inflammatory cytokines and inducing pyroptotic cell death. Pathogens, in turn, have evolved strategies to manipulate these cell death pathways, either by inhibiting them to facilitate their replication or by triggering them to evade host defenses. A deeper understanding of immunogenic cell death is crucial for developing novel immunotherapies, advancing infectious disease and cancer treatment, and revealing the complex interactions between dying cells and the immune system. This review aims to provide systematic summarization as well as recent proceedings regarding the dynamic interplay between host immune mechanisms and pathogen strategies, highlighting the intricate co-evolution of microbial virulence and host immunity.