Amphibian innate immunity and impact of environmental stress

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One third of >7000 amphibian species are threatened globally. The etiology is complex, with emerging pathogens the proximal cause. Mass amphibian die-offs resulting from fungal and viral infections suggest an environment that undermines frog immune system competency to defend against infection. At the forefront of innate immunity, the first line of defense against pathogens, is the skin epithelial barrier and the surface secreted host defense peptides (HDPs). Together they act as the interface between an organism's external and internal environments. Great diversity of HDPs is found amongst amphibians and studies have documented their antimicrobial activity against a broad-spectrum of pathogens. Recent discoveries in mammals suggest HDPs are multifaceted and play an important role in immune modulation through coordination of molecular and cellular networks. Despite this, studies on amphibian HDPs have been greatly hampered due to a lack of feasible in vitro systems to study their activity. My research program aims to address this knowledge gap in order to understand the immune modulating activity of frog HDPs on frog epithelial cells, how this activity impacts resistance to pathogens, and how these host-pathogen interactions may be affected by changes in environmental temperature as a result of climate change, leading to disease susceptibility and amphibian mortality. Recently, my lab has generated and characterized a Xenopus laevis dorsal skin epithelial cell line (Xela DS2) that is susceptible to infection with a known frog pathogen (Frog virus 3, FV3), placing my laboratory in a unique (and only) position to elucidate the molecular and functional roles of frog HDPs as immune modulators. My research will use a global systems approach from transcriptomics to intracellular pathway activation to cell function and pathogen challenge to elucidate the regulation of key immune genes (cytokines, chemokines, HDPs) and identify novel gene targets. This innovative approach will integrate HDP-driven molecular events with epithelial cell function and FV3 susceptibility, focusing on how temperature shifts associated with climate change perturb these host-pathogen dynamics at the level of the skin epithelial barrier. These novel approaches will be translated to the native North American wood frog that has evolved to withstand extreme changes in temperature to illuminate conserved and divergent mechanisms of host immunity and response to environmental stress. My research will significantly advance our understanding of how complex host-pathogen-environment interactions may be impacting Canadian frog species and will explore the utility of HDP therapy as a prevention or treatment strategy to mitigate pathogen-related amphibian deaths. These studies are instrumental for the design of pathogen prevention strategies and implementation of policies for amphibian conservation in Canada.