Acute Phase Proteins in Bacterial Infection: Structure, Mechanisms, and Clinical Significance

Abstract

C-reac ve protein (CRP), serum amyloid A (SAA), and the long pentraxin 3 (PTX3), are major acute phase proteins (APPs) of the innate immune system that mediate microbial recogni on, opsoniza on, and clearance. While structurally dis nct, all three func on as soluble pa ern recogni on receptors bridging innate and adap ve immunity. CRP, a short pentraxin, binds phosphocholine (PCho) and microbial polysaccharides, ac vates complement via C1q, and serves as a systemic biomarker of bacterial infec on. SAA, an acute-phase apolipoprotein, associates with high-density lipoproteins, modulates Toll-like receptor signaling, and binds both Gram-posi ve and Gram-nega ve bacteria, thereby enhancing opsonophagocytosis. PTX3, in contrast, is a long pentraxin produced locally at sites of infec on and ssue injury, where it binds diverse microbial ligands including fungal galactomannan and bacterial surface proteins, engages complement components (C1q, MBL, ficolin-2), and facilitates phagocytosis. Importantly, their regula on and stability differ in disease. In cys c fibrosis (CF), PTX3 is selec vely degraded in the lung by neutrophil elastase and microbial proteases, impairing local host defense, whereas CRP and SAA func oning is hindered by various microbial evasion strategies such as the forma on of a protec ve layer or strategical produc on of proteins that prevent APP binding. Collec vely, these proteins are cri cal for controlling bacterial infec ons, but their efficacy is shaped by context-specific regula on and proteoly c stability. Understanding their complementary and diverse roles provides insight into innate immunity func oning and highlights opportuni es for biomarker development and therapeu c modula on.