Infection at the vascular front: A delicate balance between defense and pathology

The vascular system is far from a passive structure during infection; rather, it serves as a dynamic regulatory network that orchestrates the delicate balance between host defense and pathology. This review establishes a vessel-centered analytical framework to systematically elucidate the continuum of balance establishment, disruption, and restoration within infectious settings. During the defensive phase, the vasculature coordinates a tightly regulated response-moderately enhancing permeability, precisely recruiting immune cells, and initiating localized coagulation-to build an effective barrier against invading pathogens. However, when pathogen virulence exceeds host control or immune responses become dysregulated, this physiological defense machinery is subverted into a self-reinforcing pathological loop characterized by leakage, hypoxia, angiogenesis, and thrombosis. This vicious cycle amplifies tissue injury and disrupts vascular integrity. Successful infection control thus depends not only on pathogen clearance but also-more critically-on reversing this pathological cycle and restoring vascular function to reestablish homeostasis. Such vascular repair entails active resolution of inflammation, regeneration of the endothelial barrier, and normalization of aberrant vascular networks. Building on an integrated summary of the mechanisms underlying balance disruption, this review further explores emerging vascular-targeted therapeutic strategies aimed at redirecting vascular responses toward repair and homeostatic restoration. This integrative perspective provides a dynamic understanding of infection-associated vasculopathies and opens new avenues for therapies designed to reestablish host equilibrium.