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The chytrid fungus, Batrachochytrium dendrobatidis (Bd), infects amphibian skin, causing chytridiomycosis, which is a contributing cause of worldwide declines and extinctions of amphibians. Relatively little is known about the roles of amphibian skin-resident immune cells, such as macrophages, in these antifungal defenses. Across vertebrates, macrophage differentiation is controlled through the activation of colony-stimulating factor-1 (CSF1) receptor by CSF1 and interleukin-34 (IL34) cytokines. While the precise roles of these respective cytokines in macrophage development remain to be fully explored, our ongoing studies indicate that frog (Xenopus laevis) macrophages differentiated by recombinant forms of CSF1 and IL34 are functionally distinct. Accordingly, we explored the roles of X. laevis CSF1- and IL34-macrophages in anti-Bd defenses. Enriching cutaneous IL34-macrophages, but not CSF1-macrophages, resulted in significant anti-Bd protection. In vitro analysis of frog macrophage-Bd interactions indicated that both macrophage subsets phagocytosed Bd. However, IL34-macrophages cocultured with Bd exhibited greater pro-inflammatory gene expression, whereas CSF1-macrophages cocultured with Bd showed greater immunosuppressive gene expression profiles. Concurrently, Bd-cocultured with CSF1-macrophages, but not IL34-macrophages, possessed elevated expression of genes associated with immune evasion. This work marks a step forward in our understanding of the roles of frog macrophage subsets in antifungal defenses. 

This is a brief review and commentary about the future studies needed in amphibian immunology in the view of the author. 

Some of the amphibian populations in Panama are demonstrating slow recovery decades after severe declines caused by the invasion of the fungal pathogenBatrachochytrium dendrobatidis(Bd). However, new species remain to be described and assessed for the mechanisms of disease resilience. We identified seven skin defense peptides from a presumably novel leopard frog species in the Tabasará range, at Buäbti (Llano Tugrí), Ngäbe-Buglé Comarca, and Santa Fe, Veraguas, Panama, herein called the Ngäbe-Buglé leopard frog. Two of the peptides were previously known: brevinin-1BLb fromRana (Lithobates) blairiand a previously hypothesized “ancestral” peptide, ranatuerin-2BPa. We hypothesized that the peptides are active againstBdand shape the microbiome such that the skin bacterial communities are more similar to those of other leopard frogs than of co-occurring host species. Natural mixtures of the collected skin peptides showed a minimum inhibitory concentration againstBdof 100 μg/ml, which was similar to that of other leopard frogs that have been tested. All sampled individuals hosted high intensity of infection withBd. We sampled nine other amphibian species in nearby habitats and found lower prevalence and intensities ofBdinfection. In addition to the pathogen load, the skin microbiomes were examined using 16S rRNA gene targeted amplicon sequencing. When compared to nine co-occurring amphibians, the Ngäbe-Buglé leopard frog had similar skin bacterial richness and anti-Bdfunction, but the skin microbiome structure differed significantly among species. The community composition of the bacterial skin communities was strongly associated with theBdinfection load. In contrast, the skin microbiome composition of the Ngäbe-Buglé leopard frog was similar to that of five North American leopard frog populations and the sympatric and congenericRana (Lithobates) warszewitschii, with 29 of the 46 core bacteria all demonstrating anti-Bdactivity in culture. Because of the highBdinfection load and prevalence in the Ngäbe-Buglé leopard frog, we suggest that treatment to reduce theBdload in this species might reduce the chytridiomycosis risk in the co-occurring amphibian community, but could potentially disrupt the evolution of skin defenses that provide a mechanism for disease resilience in this species. 

Most hosts contain few parasites, whereas few hosts contain many. This pattern, known as aggregation, is well-documented in macroparasites where parasite intensity distribution among hosts affects host–parasite dynamics. Infection intensity also drives fungal disease dynamics, but we lack a basic understanding of host–fungal aggregation patterns, how they compare with macroparasites and if they reflect biological processes. To begin addressing these gaps, we characterized aggregation of the fungal pathogenBatrachochytrium dendrobatidis(Bd) in amphibian hosts. Utilizing the slope of Taylor’s Power law, we found Bd intensity distributions were more aggregated than many macroparasites, conforming closely to lognormal distributions. We observed that Bd aggregation patterns are strongly correlated with known biological processes operating in amphibian populations, such as epizoological phase (i.e. invasion, post-invasion and enzootic), and intensity-dependent disease mortality. Using intensity-dependent mathematical models, we found evidence of evolution of host resistance based on aggregation shifts in systems persisting with Bd following disease-induced declines. Our results show that Bd aggregation is highly conserved across disparate systems and contains signatures of potential biological processes of amphibian–Bd systems. Our work can inform future modelling approaches and be extended to other fungal pathogens to elucidate host–fungal interactions and unite host–fungal dynamics under a common theoretical framework. 

As a class of vertebrates, amphibians, are at greater risk for declines or extinctions than any other vertebrate group, including birds and mammals. There are many threats, including habitat destruction, invasive species, overuse by humans, toxic chemicals and emerging diseases. Climate change which brings unpredictable temperature changes and rainfall constitutes an additional threat. Survival of amphibians depends on immune defences functioning well under these combined threats. Here, we review the current state of knowledge of how amphibians respond to some natural stressors, including heat and desiccation stress, and the limited studies of the immune defences under these stressful conditions. In general, the current studies suggest that desiccation and heat stress can activate the hypothalamus pituitary–interrenal axis, with possible suppression of some innate and lymphocyte-mediated responses. Elevated temperatures can alter microbial communities in amphibian skin and gut, resulting in possible dysbiosis that fosters reduced resistance to pathogens. This article is part of the theme issue ‘Amphibian immunity: stress, disease and ecoimmunology’. 

Global amphibian declines are compounded by deadly disease outbreaks caused by the chytrid fungus,Batrachochytrium dendrobatidis(Bd). Much has been learned about the roles of amphibian skin-produced antimicrobial components and microbiomes in controllingBd, yet almost nothing is known about the roles of skin-resident immune cells in anti-Bddefenses. Mammalian mast cells reside within and serve as key immune sentinels in barrier tissues like skin. Accordingly, we investigated the roles ofXenopus laevisfrog mast cells duringBdinfections. Our findings indicate that enrichment ofX. laevisskin mast cells confers anti-Bdprotection and ameliorates the inflammation-associated skin damage caused byBdinfection. This includes a significant reduction in infiltration ofBd-infected skin by neutrophils, promoting mucin content within cutaneous mucus glands, and preventingBd-mediated changes to skin microbiomes. Mammalian mast cells are known for their production of the pleiotropic interleukin-4 (IL4) cytokine and our findings suggest that theX. laevisIL4 plays a key role in manifesting the effects seen following cutaneous mast cell enrichment. Together, this work underscores the importance of amphibian skin-resident immune cells in anti-Bddefenses and illuminates a novel avenue for investigating amphibian host–chytrid pathogen interactions. 

Global amphibian declines are largely driven by deadly disease outbreaks caused by the chytrid fungus, Batrachochytrium dendrobatidis (Bd). In the time since these disease outbreaks were first discovered, much has been learned about the roles of amphibian skin-produced antimicrobial components and skin microbiomes in controlling Bd. Yet almost nothing is known about the roles of skin-resident immune cells in anti-Bd defenses. Notably, mammalian mast cells reside within and serve as key immune sentinels in barrier tissues like the skin. Thus, they are critical to immune recognition of pathogens and to orchestrating the ensuing immune responses. Accordingly, we investigated the roles of Xenopus laevis frog mast cells during Bd infections. Our findings indicate that enrichment of X. laevis skin mast cells confers significant anti-Bd protection and ameliorates the inflammation-associated skin damage caused by Bd infection. Moreover, enriching X. laevis mast cells promotes greater mucin content within cutaneous mucus glands and protects frogs from Bd-mediated changes to their skin microbiomes. Together, this work underlines the importance of amphibian skin-resident immune cells in anti-Bd defenses and introduces a novel approach for investigating amphibian host-chytrid pathogen interactions. 

Western palearctic salamander susceptibility to the skin disease caused by the amphibian chytrid fungusBatrachochytrium salamandrivorans(Bsal) was recognized in 2014, eliciting concerns for a potential novel wave of amphibian declines following theB. dendrobatidis(Bd) chytridiomycosis global pandemic. Although Bsal had not been detected in North America, initial experimental trials supported the heightened susceptibility of caudate amphibians to Bsal chytridiomycosis, recognizing the critical threat this pathogen poses to the North American salamander biodiversity hotspot. Here, we take stock of 10 years of research, collaboration, engagement, and outreach by the North American Bsal Task Force. We summarize main knowledge and conservation actions to both forestall and respond to Bsal invasion into North America. We address the questions: what have we learned; what are current challenges; and are we ready for a more effective reaction to Bsal’s eventual detection? We expect that the many contributions to preemptive planning accrued over the past decade will pay dividends in amphibian conservation effectiveness and can inform future responses to other novel wildlife diseases and extreme threats.