Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
Many amphibian populations are declining worldwide, and infectious diseases are a leading cause. Given the eminent threat infectious diseases pose to amphibian populations, there is a need to understand the host-pathogen-environment interactions that govern amphibian susceptibility to disease and mortality events. However, using animals in research raises an ethical dilemma, which is magnified by the alarming rates at which many amphibian populations are declining. Thus, in vitro study systems such as cell lines represent valuable tools for furthering our understanding of amphibian immune systems. In this review, we curate a list of the amphibian cell lines established to date (the amphibian invitrome), highlight how research using amphibian cell lines has advanced our understanding of the amphibian immune system, anti-ranaviral defence mechanisms, and Batrachochytrium dendrobatidis replication in host cells, and offer our perspective on how future use of amphibian cell lines can advance the field of amphibian immunology.
Fig. 1. Timeline of amphibian cell line development and select immunological milestones. Since the development of the first reported amphibian cell line in 1964, over 150 distinct amphibian cell lines have been developed. The number of novel anuran and caudatan cell lines reported, as well as the cumulative number of amphibian cell lines, are given for each year. Amphibian cell lines have been used to study host-pathogen interactions since they were first developed and continue to support our understanding of amphibian immune responses today. Abbreviations: Bd, Batrachochytrium dendrobatidis; FV3, frog virus 3; TNF, tumour necrosis factor.
Fig. 2. The current state of the amphibian invitrome. A. A cladogram depicting the evolutionary relationships between extant amphibian orders and families, adapted from AmphibiaWeb's Family Phylogeny (AmphibiaWeb, 2022). Bolded numbers in square brackets indicate the number of reported cell lines developed from members of each family, if any. B. A pie chart summarizing the tissue origins of the reported amphibian cell lines. C. A pie chart summarizing the storage and availability status of the reported amphibian cell lines into cell lines in the curated invitrome (cell lines held in collections of formal agencies), those that have been recently used in the literature but are not curated and are likely in the informally shared invitrome (informally shared between researchers), and those that are likely in the zombie invitrome (cell lines that have been described in publications but do not appear to be used or stored any longer).
Fig. 3. Recent advances in amphibian immunology made using amphibian cell lines. In the past decade (2012–2022), immunological studies relying on amphibian cell lines have focused on monitoring responses to poly(I:C) (violet, described in Section 3.2.1), FV3 (blue, described in Section 3.3.1.1), ADRV (green, described in Section 3.3.1.2), and Bd (yellow, described in Section 3.3.2). While A6 continues to be the most widely used amphibian cell line, several recently developed cell lines from varied species and tissue origins have made major contributions. Abbreviations: ADRV, Andrias davidianus ranavirus; Bcl-xL, B-cell lymphoma-extra large; Bd, Batrachochytrium dendrobatidis; Bid, BH3-interacting domain death agonist; SR-A, Class A Scavenger Receptor; FV3, frog virus 3; IFN, interferon; poly(I:C), polyinosinic:polycytidylic acid; vβHSD, viral β-hydroxysteroid dehydrogenase; vCARD, viral caspase activation and recruitment domain-containing protein; vIF-2α, viral eukaryotic translation initiation factor 2 subunit 1.
