Compartmental immunity in intra-abdominal infection: from peritoneal defense to systemic sepsis

Complicated intra-abdominal infection (cIAI) represents a common and challenging surgical emergency that frequently progresses from localized infection to intra-abdominal sepsis (IAS), leading to rapid clinical deterioration, early organ dysfunction, and unfavorable outcomes. However, the immunological mechanisms underlying these clinical behaviors remain incompletely understood. This review advances a compartment-oriented immunopathological framework to explain the unique behavior of abdominal infection across the cIAI-IAS spectrum. The peritoneal cavity is not an immunologically passive space but a highly specialized immune compartment pre-equipped with fat-associated lymphoid clusters (milky spots), peritoneal resident macrophages (PRMs), B1 cells, and innate lymphoid cells (ILCs). Upon intra-abdominal contamination, this regional immune network enables rapid and high-intensity local inflammatory responses that initially favor containment of polymicrobial infection. However, inadequate or delayed multimodal intervention, together with unfavorable host conditions such as advanced age, immunosuppression, comorbidities, and high disease severity, may permit excessive inflammatory amplification and peritoneal barrier failure within this confined anatomical space. As a consequence, pathogen- and injury-associated signals disseminate rapidly through vascular and lymphatic pathways, driving progression from cIAI to IAS. Together, this compartment-oriented perspective challenges the traditionally source control-focused understanding of cIAI by highlighting the critical role of peritoneal immune compartmentalization, opening avenues for earlier risk stratification and immunologically informed, stratified intervention strategies across the full cIAI-IAS spectrum.