Relationship between local neuroimmune impairment and diabetic foot: the immunocompromised district theory

Diabetic foot (DF) can be defined as an infection and/or an ulceration with or without destruction of deep tissues associated with neurological abnormalities and varying degrees of peripheral vascular disease of the lower limb in patients with diabetes. Both neuropathy and vascular disease, along with the well-known impairment of immune function in patients with diabetes, contribute to polymicrobial foot infections, which further aggravate the already severe clinical manifestations of diabetes.The immunocompromised district (ICD) is a novel pathogenic concept referring to a site in which there is an obstacle to the normal trafficking of immunocompetent cells through lymphatic channels, and/or interference with the signals that neuropeptides and neurotransmitters, released by peripheral nerves, send to cell membrane receptors of immunocompetent cells. These loci minoris resistentiae have the propensity to develop a secondary disease, which may occur after an extremely variable length of time.In this work, we provide an overview of etiopathogenetic mechanisms of DF and propose a unifying view of this topic based on the concept of the ICD.