Human defensins and LL-37 in mucosal immunity

Abstract

Defensins are widespread in nature and have activity against a broad range of pathogens. Defensins have direct antimicrobial effects and also modulate innate and adaptive immune responses. We consider the role of human defensins and the cathelicidin LL-37 in defense of respiratory, gastrointestinal, and genitourinary tracts and the oral cavity, skin, and eye. Human beta-defensins (hBDs) and human defensins 5 and 6 (HD5 and -6) are involved most obviously in mucosal responses, as they are produced principally by epithelial cells. Human alpha-defensins 1-4 (or HNPs 1-4) are produced principally by neutrophils recruited to the mucosa. Understanding the biology of defensins and LL-37 is the beginning to clarify the pathophysiology of mucosal inflammatory and infectious diseases (e.g., Crohn's disease, atopic dermatitis, lung or urinary infections). Challenges for these studies are the redundancy of innate defense mechanisms and the presence and interactions of many innate defense proteins in mucosal secretions.

Figure 1

Schematic overview of BD and LL‐37 production by respiratory epithelia.

Figure 2

Overview of production and actions of HNPs. Note that macrophages (and possibly other cells) can take up HNPs from the extracellular milieu and use them to inhibit intracellular pathogens.

Figure 3

Overview of production of LL‐37 by neutrophils and actions of LL‐37.