Phagocytes as Key Players: Unveiling Cell-Death Patterns Induced by Vaccines in Combating Infectious Diseases

This chapter delves into an in-depth analysis of the central role played by phagocytes—particularly macrophages—in modulating immune responses elicited by vaccines against infectious diseases. It emphasizes the functional plasticity and immunological versatility of macrophages, focusing on their capacity to integrate signals from vaccine-induced cell-death pathways, including apoptosis, necrosis, and pyroptosis. These cell-death modalities are examined in the context of their capacity to influence antigen availability, inflammatory milieu, and subsequent immune activation. Here, macrophages are further characterized beyond their canonical role in pathogen clearance, with detailed attention to their contributions to antigen processing and presentation, cytokine and chemokine secretion, tissue remodeling, and the orchestration of both innate and adaptive immune responses. Particular emphasis is placed on their immunoregulatory functions in viral pathogenesis and vaccine responsiveness. The chapter also interrogates the bidirectional crosstalk between vaccine-induced cell death and macrophage activation states, delineating how this interplay shapes immunogenicity and vaccine efficacy. It explores the translational implications of these findings for rational vaccine design, including strategies to potentiate macrophage-mediated immunomodulation through targeted adjuvants or delivery systems. By elucidating the mechanistic underpinnings of macrophage involvement in vaccine-induced immunity, this chapter aims to inform the development of next-generation vaccines that leverage programmed cell-death pathways to optimize immunological outcomes and therapeutic efficacy.