Immune Response to Fungi in Diabetic Patients with Invasive Fungal Rhinosinusitis.

This article aims to review the literature regarding the immune response to fungi in diabetic patients with invasive fungal rhinosinusitis. Systematic searches of Medline, EMBASE, and Cochrane Library databases were performed to include articles from 1988 to 2019 which assessed 'immune response to fungi in normal host', 'immune deficiency in diabetes mellitus', or 'immune response to fungi in diabetic patients'. Fungal cell wall activated pattern recognition receptors, resulting in recruitment of innate immune cells and an adaptive immune response. In diabetes mellitus, the expression of class I major histocompatibility complex was reduced. A hyperglycemic state decreased vascular dilation and the formation of neutrophil extracellular traps. The structure of complement was altered with consequent inhibition of complement fixation to bacteria. The balance between complement activation and restriction was broken. Hyperglycemia activated protein kinase C which inhibited neutrophil migration, decreased production of polymorphonuclear cells, decreased chemotaxis and decreased phagocytic activity. Germination and filamentous growth of the fungus within a diabetic host caused angioinvasion, vascular thrombosis and necrosis. Patients with diabetic ketoacidosis had elevated levels of serum iron which regulated endothelial cell damage. Iron and the overexpression of glucose-induced glucose-regulated protein 78 enhanced the susceptibility of endothelial cells to fungi and induced fungal invasion. In summary, associations among the immunopathology of diabetes, the pathophysiology of fungal infections, and the therapeutic outcomes must be considered in clinical practice. In diabetic patients, both the humoral and cellular immune responses of innate and adaptive immune systems were defective. Treatments should aim for the immune function restoration.