Defensins represent an ancient highly conserved part of the innate immune system. Most of these small endogenous peptides possess broad-spectrum antimicrobial activity as well as immunomodulatory functions. In humans, granulocytes, as well as Paneth cells, secrete different alpha-defensins whereas beta-defensins are expressed by epithelial surfaces throughout the body. Beta-defensin 2, consists of 64 amino acids and has a molecular weight of 7 kDa.
Defensins exert a variable degree of antimicrobial activity against bacteria, fungi, and some enveloped viruses. Vertebrate defensins are classified as α- or β-defensins, based on their pattern of disulfide bridges. Nine human defensins of epithelial origin have been found, three of them being beta-defensins (HBD-1, -2, and -3). The expression of beta-defensins is induced by the pro-inflammatory cytokines and also through microorganisms (e.g., E. coli, H. pylori, or P. aeruginosa).
As shown in vitro HBD2 has strong antimicrobial and immunomodulatory functions and is induced by inflammatory stimuli or exogenous microbial substances. HBD2 promotes intestinal wound healing and angiogenesis in vitro and can act as a chemoattractant for dendritic cells (DCs), monocytes, and T-cells through interaction with the chemokine receptor 2 (CCR2) and 6 (CCR6). Thus, in addition to a lack of mucosal antibacterial activity low defensin expression may also translate into a repressed anti-inflammatory activity. Together, these data provide evidence for an important role of defensins, including hBD2, in IBD disease pathogenesis and potential therapy.
A beta-defensin 2 deficiency can, for example, be observed in the intestinal mucous of patients with Crohn’s disease. The defense system of the mucous membrane is therefore restricted and allows an increased invasion of bacteria, which could possibly lead to a typical infection in Crohn’s disease patients.