Defensins: A Double-Edged Sword in Host Immunity

Defensins are a major family of host defense peptides expressed predominantly in neutrophils and epithelial cells. Their broad antimicrobial activities and multifaceted immunomodulatory functions have been extensively studied, cementing their role in innate immunity as a core host-protective component against bacterial, viral and fungal infections. More recent studies, however, paint defensins in a bad light such that they are “alleged” to promote viral and bacterial infections in certain biological settings. This mini review summarizes the latest findings on the potential pathogenic properties of defensins against the backdrop of their protective roles in antiviral and antibacterial immunity. Further, a succinct description of both tumor-proliferative and -suppressive activities of defensins is also given to highlight their functional and mechanistic complexity in antitumor immunity. We posit that given an enabling environment defensins, widely heralded as the “Swiss army knife,” can function as a “double−edged sword” in host immunity.