Avian cathelicidins: paradigms for the development of anti-infectives

The broad-spectrum defense system based on host defense peptides (HDPs) is evolutionary very old and many invertebrates rely on this system for protection from bacterial infections. However, in vertebrates the system remained important in spite of the superposition of a very sophisticated adaptive immune system. The cathelicidins comprise a major group of HDPs in mammals. About six years ago it was first described that cathelicidins are also present in birds. Here we review the properties and biological activities of the recently discovered avian cathelicidins and their potential to be used as a paradigm for the development of anti-infectives. Like the mammalian cathelicidins, avian cathelicidins exert direct antimicrobial activities but can also selectively boost host immune responses by regulation of cytokine production and recruitment of immune cells. In addition, it was found that chicken cathelicidins bind endotoxins and dampen the endotoxin-mediated inflammatory response. Molecular dissection has allowed identification of different structural elements involved in bacterial killing and immunomodulation. These studies have enabled the design of small HDP-based antibiotics with specific functions, i.e. having primarily immunomodulatory or antimicrobial activities. Since the immunomodulatory effects may, to a certain degree, be species-specific, we hypothesize that poultry-specific antibiotics can be developed based on avian cathelicidins.