The Multiple Faces of Host Defence Peptides and Proteins

AMPs can reduce proinflammatory responses, hence preventing the cytokine storm and organ damage seen during sepsis. AMPs may also act by other more subtle cell-specific mechanisms. For example, they may interfere with the Toll-like receptor 4 (TLR4) recognition system by disturbing the local membrane environment of the receptor, modifying its activation state, and leading to the suppression of cytokine production and the modulation of the inflammatory response. Increased knowledge of the structural prerequisites for LPS and/or cell interactions could lead to the development of new drugs to neutralize and modulate the endotoxic activities of LPS.  -Defensins comprise one of the largest groups of HDPs, found in the skin and on other epithelial surfaces. These cysteineconstrained peptides selectively kill many different microbes, including bacteria, yeasts and viruses. In recent years, multiple other roles for defensins have been uncovered. Semple and Dorin [9] review the recent advances on this important family of HDPs. With respect to their immunomodulatory actions, defensins may bind to several cell-surface receptors and enhance the immune response. Recent data, however, indicate that these molecules may also attenuate the immune response. Hence, it is apparent that defensins exAntimicrobial peptides (AMPs) constitute an extensive family of molecules which provide a first line of defence against invading microbes at epithelial surfaces as well as in blood [1–5] . It has become increasingly evident that many AMPs, such as defensins and cathelicidins, are multifunctional and mediate multiple immunomodulatory effects [6, 7] . This has motivated the broader definition, host defence peptides (HDPs), for these members of the innate immune system. The family of host defence molecules has recently been shown to encompass not only ‘classic’ AMPs, but also various bioactive peptides and proteins with antimicrobial activities. Thus, a complex picture is emerging where a temporospatial expression of multiple host defence molecules not only mediates a direct interaction with microbes, but where there is simultaneous ‘tuning’ and control of various components of adaptive and innate immunity. In this issue of the Journal of Innate Immunity , we focus on various aspects of the intriguing multifunctionality of HDPs. The binding of AMPs to lipopolysaccharide (LPS) is a critical step in their antimicrobial action, but this interaction also implicates immunomodulatory roles. In the first review, contributed by Pulido et al. [8] , the various mechanisms underlying the antiendotoxic effects of many AMPs are described in detail. By neutralizing circulating endotoxins, Published online: May 22, 2012 Journal of Innate Immunity