Antimicrobial peptides, also more broadly termed host defense peptides (HDPs) are widely conserved across the plant and animal kingdoms, serving as front-line innate immune molecules against invading pathogens. Recent years have seen substantial growth in HDP research, with a large number of publications highlighting their functional versatility. In addition to their direct antimicrobial function, many studies have reported their importance in inflammation and immunomodulation. Hence, this has led to adopting a more comprehensive designation as “host defense peptides” rather than simply “antimicrobial peptides”.

HDPs form an integral part of immune systems, contributing to the shape and complex nature of host responses to infection. For example, the mammalian alpha- and beta-defensins are important HDP families that play central roles in innate defense against pathogenic bacteria, fungi, and viruses, as well as regulating aspects of the immune response. Insights into HDP structure and function have revolutionized our understanding of HDP biology and provided a platform for the development of novel therapeutics. However, despite these achievements, there are several challenging obstacles for HDP research and its application, including limitations in specificity and stability, issues arising from biphasic immunomodulatory effects and restrictive therapeutic windows.

In this Research Topic, we aim to highlight recent advances in HDP research in order to appreciate their diversity and complexity, with a particular emphasis on mechanisms of action from an immunological perspective, as well as applications of HDPs beyond direct antimicrobial activity. We call for Original Research (experimental or computational), current state-of-the-art Reviews, Perspectives, Brief Reports, and Commentaries. Research that emphasizes the structural and functional diversity of HDPs and addresses the existing challenges to the field is encouraged.

Potential topics include but are not limited to the following:

● Insights into HDP structure-function relationship and evolution in host defense against pathogens.
● Maximizing HDP potential to combat antibiotic resistance (particularly HDP optimization and engineering).
● HDP-mediated immunomodulation (including signaling and inflammatory diseases).
● Novel HDP discoveries.
● Novel immune functions of HDPs (including anticancer) with mechanistic insights.

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Frontiers in Immunology

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