XB-ART-56898
Front Immunol
2018 Sep 12;9:3128. doi: 10.3389/fimmu.2018.03128.
Show Gene links
Show Anatomy links
Frog Skin Innate Immune Defences: Sensing and Surviving Pathogens.
Varga JFA
,
Bui-Marinos MP
,
Katzenback BA
.
???displayArticle.abstract???
Amphibian skin is a mucosal surface in direct and continuous contact with a microbially diverse and laden aquatic and/or terrestrial environment. As such, frog skin is an important innate immune organ and first line of defence against pathogens in the environment. Critical to the innate immune functions of frog skin are the maintenance of physical, chemical, cellular, and microbiological barriers and the complex network of interactions that occur across all the barriers. Despite the global decline in amphibian populations, largely as a result of emerging infectious diseases, we understand little regarding the cellular and molecular mechanisms that underlie the innate immune function of amphibian skin and defence against pathogens. In this review, we discuss the structure, cell composition and cellular junctions that contribute to the skin physical barrier, the antimicrobial peptide arsenal that, in part, comprises the chemical barrier, the pattern recognition receptors involved in recognizing pathogens and initiating innate immune responses in the skin, and the contribution of commensal microbes on the skin to pathogen defence. We briefly discuss the influence of environmental abiotic factors (natural and anthropogenic) and pathogens on the immunocompetency of frog skin defences. Although some aspects of frog innate immunity, such as antimicrobial peptides are well-studied; other components and how they contribute to the skin innate immune barrier, are lacking. Elucidating the complex network of interactions occurring at the interface of the frog's external and internal environments will yield insight into the crucial role amphibian skin plays in host defence and the environmental factors leading to compromised barrier integrity, disease, and host mortality.
???displayArticle.pubmedLink??? 30692997
???displayArticle.pmcLink??? PMC6339944
???displayArticle.link??? Front Immunol
Species referenced: Xenopus
Genes referenced: egfr glp1r levi magainins pgla stat3 tlr5 xt6l
GO keywords: innate immune response
???attribute.lit??? ???displayArticles.show???
|
|
Figure 1. The physical, chemical, cellular, and microbiological innate immune barriers of frog skin. Frog skin, which is mucosal in nature, contains physical, chemical, cellular, and microbiological barriers that work together in defence against pathogen assault. Frog skin is composed of an epidermal and dermal layer, containing resident immune cells throughout the layers. The epidermis is comprised of stratified squamous epithelial cells in three distinct layers: the stratum corneum (1), stratum spinosum (2), and stratum germinativum. The dermis is largely comprised of connective tissue formed by collagenous fibres (black lines) in two layers, the spongious dermis (4) and the compact dermis (6), connected by collagenous columns (white star). In mainly terrestrial frogs, the Eberth-Kastschenko layer (5, thick blue line) separates the spongious dermal layer and compact dermal layer. Glands within the dermal layer include granular glands (a), mucosal glands (b), and small mixed glands (c) that secrete a slew of compounds, including mucus and antimicrobial peptides. Commensal bacteria overlay the frog skin layers, forming the microbiological barrier. The image was, in part, created with the aid of BioRender. |
References [+] :
Abedi,
A histological and ultrastructural study of the skin of rainbow trout (Oncorhynchus mykiss) alevins exposed to different levels of ultraviolet B radiation.
2015, Pubmed
Abedi, A histological and ultrastructural study of the skin of rainbow trout (Oncorhynchus mykiss) alevins exposed to different levels of ultraviolet B radiation. 2015, Pubmed
Albiol Matanic, Antiviral activity of antimicrobial cationic peptides against Junin virus and herpes simplex virus. 2004, Pubmed
Alibardi, Structural and immunocytochemical characterization of keratinization in vertebrate epidermis and epidermal derivatives. 2006, Pubmed
Álvarez, Damage-associated molecular patterns and their role as initiators of inflammatory and auto-immune signals in systemic lupus erythematosus. 2017, Pubmed
Angel, Ultrastructural patterns of secretory activity in poison cutaneous glands of larval and juvenile Dendrobates auratus (Amphibia, Anura). 2003, Pubmed
Antwis, Ex situ diet influences the bacterial community associated with the skin of red-eyed tree frogs (Agalychnis callidryas). 2014, Pubmed
Azevedo, Dermal collagen organization in Bufo ictericus and in Rana catesbeiana integument (Anuran, Amphibian) under the evaluation of laser confocal microscopy. 2006, Pubmed
Azevedo, Hyaluronan in the epidermal and the dermal extracellular matrix: its role in cutaneous hydric balance and integrity of anuran integument. 2007, Pubmed
Bagnara, The dermal chromatophore unit. 1968, Pubmed
Bechinger, Detergent-like actions of linear amphipathic cationic antimicrobial peptides. 2006, Pubmed
Bechinger, Structure and orientation of the antibiotic peptide magainin in membranes by solid-state nuclear magnetic resonance spectroscopy. 1993, Pubmed , Xenbase
Belden, Panamanian frog species host unique skin bacterial communities. 2015, Pubmed
Berger, Life cycle stages of the amphibian chytrid Batrachochytrium dendrobatidis. 2005, Pubmed
Biniek, Solar UV radiation reduces the barrier function of human skin. 2012, Pubmed
Bletz, Skin microbiota differs drastically between co-occurring frogs and newts. 2017, Pubmed
Boudinot, A tetrapod-like repertoire of innate immune receptors and effectors for coelacanths. 2014, Pubmed
Braff, Cutaneous defense mechanisms by antimicrobial peptides. 2005, Pubmed
Brenes, Transmission of ranavirus between ectothermic vertebrate hosts. 2014, Pubmed
Brizzi, Specialized mucous glands and their possible adaptive role in the males of some species of Rana (Amphibia, Anura). 2002, Pubmed
Brubaker, Innate immune pattern recognition: a cell biological perspective. 2015, Pubmed
Brunetti, Odorous secretions in anurans: morphological and functional assessment of serous glands as a source of volatile compounds in the skin of the treefrog Hypsiboas pulchellus (Amphibia: Anura: Hylidae). 2016, Pubmed
Brunner, Transmission dynamics of the amphibian ranavirus Ambystoma tigrinum virus. 2007, Pubmed
Brutyn, Batrachochytrium dendrobatidis zoospore secretions rapidly disturb intercellular junctions in frog skin. 2012, Pubmed , Xenbase
Calhoun, Role of Antimicrobial Peptides in Amphibian Defense Against Trematode Infection. 2016, Pubmed
Cario, Intestinal epithelial TOLLerance versus inTOLLerance of commensals. 2005, Pubmed
Carrillo-Farga, Langerhans-like cells in amphibian epidermis. 1990, Pubmed
Cassano, Atrazine increases the sodium absorption in frog (Rana esculenta) skin. 2006, Pubmed
Castell-Rodríguez, Non-specific esterase-positive dendritic cells in epithelia of the frog Rana pipiens. 2001, Pubmed
Chang, Xclaudin 1 is required for the proper gastrulation in Xenopus laevis. 2010, Pubmed , Xenbase
Chen, The skin microbiome: current perspectives and future challenges. 2013, Pubmed
Chinchar, Inactivation of viruses infecting ectothermic animals by amphibian and piscine antimicrobial peptides. 2004, Pubmed
Chow, RIG-I and Other RNA Sensors in Antiviral Immunity. 2018, Pubmed
Cone, Barrier properties of mucus. 2009, Pubmed
Conlon, The contribution of skin antimicrobial peptides to the system of innate immunity in anurans. 2011, Pubmed
Conlon, Evaluation of the skin peptide defenses of the Oregon spotted frog Rana pretiosa against infection by the chytrid fungus Batrachochytrium dendrobatidis. 2013, Pubmed
Conlon, Peptides with potent cytolytic activity from the skin secretions of the North American leopard frogs, Lithobates blairi and Lithobates yavapaiensis. 2009, Pubmed
Cramp, First line of defence: the role of sloughing in the regulation of cutaneous microbes in frogs. 2014, Pubmed
Cramp, Exploring the link between ultraviolet B radiation and immune function in amphibians: implications for emerging infectious diseases. 2018, Pubmed
Cuesta, The antimicrobial peptide hepcidin exerts an important role in the innate immunity against bacteria in the bony fish gilthead seabream. 2008, Pubmed
Daly, Biologically active substances from amphibians: preliminary studies on anurans from twenty-one genera of Thailand. 2004, Pubmed
Daly, Thirty years of discovering arthropod alkaloids in amphibian skin. 1998, Pubmed
Daly, Ernest Guenther award in chemistry of natural products. Amphibian skin: a remarkable source of biologically active arthropod alkaloids. 2003, Pubmed
Daly, Further classification of skin alkaloids from neotropical poison frogs (Dendrobatidae), with a general survey of toxic/noxious substances in the amphibia. 1987, Pubmed
Daly, Alkaloids from amphibian skin: a tabulation of over eight-hundred compounds. 2005, Pubmed
Daszak, Emerging infectious diseases and amphibian population declines. 1999, Pubmed
Davidson, Effects of chytrid and carbaryl exposure on survival, growth and skin peptide defenses in foothill yellow-legged frogs. 2007, Pubmed
Davis, The inflammasome NLRs in immunity, inflammation, and associated diseases. 2011, Pubmed
De Jesús Andino, Long term effects of carbaryl exposure on antiviral immune responses in Xenopus laevis. 2017, Pubmed , Xenbase
Delfino, Granular cutaneous glands in the frog Physalaemus biligonigerus (Anura, Leptodactylidae): comparison between ordinary serous and 'inguinal' glands. 1999, Pubmed
Denèfle, Localization of fibronectin in the frog skin. 1993, Pubmed
Di Grazia, The Frog Skin-Derived Antimicrobial Peptide Esculentin-1a(1-21)NH2 Promotes the Migration of Human HaCaT Keratinocytes in an EGF Receptor-Dependent Manner: A Novel Promoter of Human Skin Wound Healing? 2015, Pubmed
Dubaissi, Functional characterization of the mucus barrier on the Xenopus tropicalis skin surface. 2018, Pubmed , Xenbase
Dubaissi, A secretory cell type develops alongside multiciliated cells, ionocytes and goblet cells, and provides a protective, anti-infective function in the frog embryonic mucociliary epidermis. 2014, Pubmed , Xenbase
Duplantier, The Human Cathelicidin Antimicrobial Peptide LL-37 as a Potential Treatment for Polymicrobial Infected Wounds. 2013, Pubmed
Dürr, LL-37, the only human member of the cathelicidin family of antimicrobial peptides. 2006, Pubmed
Eley, Activities of the frog skin peptide, ascaphin-8 and its lysine-substituted analogs against clinical isolates of extended-spectrum beta-lactamase (ESBL) producing bacteria. 2008, Pubmed
Ellison, Anchoring filaments of the amphibian epidermal-dermal junction traverse the basal lamina entirely from the plasma membrane of hemidesmosomes to the dermis. 1984, Pubmed
Emerson, "RED-LEG"-AN INFECTIOUS DISEASE OF FROGS. 1905, Pubmed
Engelhardt, Coupled secretion of chloride and mucus in skin of Xenopus laevis: possible role for CFTR. 1994, Pubmed , Xenbase
Fan, Comparative transcriptome analyses reveal the genetic basis underlying the immune function of three amphibians' skin. 2017, Pubmed
Farquhar, Cell junctions in amphibian skin. 1965, Pubmed
Ferreira, The effect of low external pH on properties of the paracellular pathway and junctional structure in isolated frog skin. 1982, Pubmed
Fitzpatrick, Similarity and differentiation between bacteria associated with skin of salamanders (Plethodon jordani) and free-living assemblages. 2014, Pubmed
Forzán, Pathogenesis of Frog Virus 3 ( Ranavirus, Iridoviridae) Infection in Wood Frogs ( Rana sylvatica). 2017, Pubmed
Fritz, Innate immune recognition at the epithelial barrier drives adaptive immunity: APCs take the back seat. 2008, Pubmed
Furuse, Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice. 2002, Pubmed
Gammill, Norepinephrine depletion of antimicrobial peptides from the skin glands of Xenopus laevis. 2012, Pubmed , Xenbase
Gibb, Frogs host faecal bacteria typically associated with humans. 2017, Pubmed
Gilbertson, Immunosuppression in the northern leopard frog (Rana pipiens) induced by pesticide exposure. 2003, Pubmed
Gray, Ecology and pathology of amphibian ranaviruses. 2009, Pubmed , Xenbase
Grayfer, Immune evasion strategies of ranaviruses and innate immune responses to these emerging pathogens. 2012, Pubmed , Xenbase
Gregorio, Plasmacytoid dendritic cells sense skin injury and promote wound healing through type I interferons. 2010, Pubmed
Günther, The first line of defence: insights into mechanisms and relevance of phagocytosis in epithelial cells. 2018, Pubmed
Hancock, The immunology of host defence peptides: beyond antimicrobial activity. 2016, Pubmed
Hancock, The role of antimicrobial peptides in animal defenses. 2000, Pubmed
Hancock, Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. 2006, Pubmed
Haney, Solution NMR studies of amphibian antimicrobial peptides: linking structure to function? 2009, Pubmed
Hao, Amphibian cathelicidin fills the evolutionary gap of cathelicidin in vertebrate. 2012, Pubmed
Harmouche, Lipid-Mediated Interactions between the Antimicrobial Peptides Magainin 2 and PGLa in Bilayers. 2018, Pubmed
Hasan, Mechanism of Initial Stage of Pore Formation Induced by Antimicrobial Peptide Magainin 2. 2018, Pubmed , Xenbase
Haslam, From frog integument to human skin: dermatological perspectives from frog skin biology. 2014, Pubmed
Hirata, Activation of innate immune defense mechanisms by signaling through RIG-I/IPS-1 in intestinal epithelial cells. 2007, Pubmed
Holmes, In vitro studies on the control of myoepithelial cell contraction in the granular glands of Xenopus laevis skin. 1978, Pubmed , Xenbase
Holthausen, An Amphibian Host Defense Peptide Is Virucidal for Human H1 Hemagglutinin-Bearing Influenza Viruses. 2017, Pubmed
Horton, Skin xenograft rejection in Xenopus--immunohistology and effect of thymectomy. 1992, Pubmed , Xenbase
Hovey, Sequestered Alkaloid Defenses in the Dendrobatid Poison Frog Oophaga pumilio Provide Variable Protection from Microbial Pathogens. 2018, Pubmed
Huang, Comparative transcriptome analyses of seven anurans reveal functions and adaptations of amphibian skin. 2016, Pubmed
Imura, Magainin 2 in action: distinct modes of membrane permeabilization in living bacterial and mammalian cells. 2008, Pubmed , Xenbase
Insuela, Glucagon and glucagon-like peptide-1 as novel anti-inflammatory and immunomodulatory compounds. 2017, Pubmed
Ishii, Phylogenetic and expression analysis of amphibian Xenopus Toll-like receptors. 2007, Pubmed , Xenbase
Jacques, Xenopus-FV3 host-pathogen interactions and immune evasion. 2017, Pubmed , Xenbase
Jani, Host and Aquatic Environment Shape the Amphibian Skin Microbiome but Effects on Downstream Resistance to the Pathogen Batrachochytrium dendrobatidis Are Variable. 2018, Pubmed
Katzenback, Regulation of the Rana sylvatica brevinin-1SY antimicrobial peptide during development and in dorsal and ventral skin in response to freezing, anoxia and dehydration. 2014, Pubmed
Ketola-Pirie, Cold- and heat-shock induction of new gene expression in cultured amphibian cells. 1983, Pubmed , Xenbase
Kim, Apoptosis of human intestinal epithelial cells after bacterial invasion. 1998, Pubmed
Kirschner, Barriers and more: functions of tight junction proteins in the skin. 2012, Pubmed
König, The diversity and evolution of anuran skin peptides. 2015, Pubmed
Koubourli, Immune roles of amphibian (Xenopus laevis) tadpole granulocytes during Frog Virus 3 ranavirus infections. 2017, Pubmed , Xenbase
Kress, CRAMP deficiency leads to a pro-inflammatory phenotype and impaired phagocytosis after exposure to bacterial meningitis pathogens. 2017, Pubmed
Krynak, Larval Environment Alters Amphibian Immune Defenses Differentially across Life Stages and Populations. 2015, Pubmed
Kueneman, Probiotic treatment restores protection against lethal fungal infection lost during amphibian captivity. 2016, Pubmed
Kueneman, The amphibian skin-associated microbiome across species, space and life history stages. 2014, Pubmed
Kwon, Structural organization and expression of the gaegurin 4 gene of Rana rugosa. 2000, Pubmed , Xenbase
Kwong, Evidence for a role of tight junctions in regulating sodium permeability in zebrafish (Danio rerio) acclimated to ion-poor water. 2013, Pubmed
Ladram, Antimicrobial peptides from frog skin: biodiversity and therapeutic promises. 2016, Pubmed
Laing, A genomic view of the NOD-like receptor family in teleost fish: identification of a novel NLR subfamily in zebrafish. 2008, Pubmed
Lan, Structural contributions to the intracellular targeting strategies of antimicrobial peptides. 2010, Pubmed
Lande, Cationic antimicrobial peptides in psoriatic skin cooperate to break innate tolerance to self-DNA. 2015, Pubmed
Larsen, Role of cutaneous surface fluid in frog osmoregulation. 2013, Pubmed
Lau, Selective constraint acting on TLR2 and TLR4 genes of Japanese Rana frogs. 2018, Pubmed
Lau, Transcriptome analyses of immune tissues from three Japanese frogs (genus Rana ) reveals their utility in characterizing major histocompatibility complex class II. 2017, Pubmed
Lei-Leston, Epithelial Cell Inflammasomes in Intestinal Immunity and Inflammation. 2017, Pubmed
Levi, The distribution of E-cadherin during Xenopus laevis development. 1991, Pubmed , Xenbase
Lillywhite, Water relations of tetrapod integument. 2006, Pubmed
Lillywhite, Physiological correlates of basking in amphibians. 1975, Pubmed , Xenbase
Lillywhite, A comparative study of integumentary mucous secretions in amphibians. 1975, Pubmed
Liu, A short peptide from frog skin accelerates diabetic wound healing. 2014, Pubmed
Loffredo, Membrane perturbing activities and structural properties of the frog-skin derived peptide Esculentin-1a(1-21)NH2 and its Diastereomer Esc(1-21)-1c: Correlation with their antipseudomonal and cytotoxic activity. 2017, Pubmed
Longo, Seasonal and ontogenetic variation of skin microbial communities and relationships to natural disease dynamics in declining amphibians. 2015, Pubmed
Lorin, The antimicrobial peptide dermaseptin S4 inhibits HIV-1 infectivity in vitro. 2005, Pubmed
Loudon, Interactions between amphibians' symbiotic bacteria cause the production of emergent anti-fungal metabolites. 2014, Pubmed
Luca, Esculentin(1-21), an amphibian skin membrane-active peptide with potent activity on both planktonic and biofilm cells of the bacterial pathogen Pseudomonas aeruginosa. 2013, Pubmed
Ludtke, Membrane pores induced by magainin. 1996, Pubmed , Xenbase
Madison, Characterization of Batrachochytrium dendrobatidis Inhibiting Bacteria from Amphibian Populations in Costa Rica. 2017, Pubmed
Majer, Nucleic acid-sensing TLRs: trafficking and regulation. 2017, Pubmed
Mall, Role of cilia, mucus, and airway surface liquid in mucociliary dysfunction: lessons from mouse models. 2008, Pubmed
Mangoni, Antimicrobial peptides and wound healing: biological and therapeutic considerations. 2016, Pubmed
Mangoni, The synthesis of antimicrobial peptides in the skin of Rana esculenta is stimulated by microorganisms. 2001, Pubmed
Manzo, Folded structure and insertion depth of the frog-skin antimicrobial Peptide esculentin-1b(1-18) in the presence of differently charged membrane-mimicking micelles. 2014, Pubmed
Marenah, Characterization of naturally occurring peptides in the skin secretion of Rana pipiens frog reveal pipinin-1 as the novel insulin-releasing agent. 2005, Pubmed
Marshall, The role of mast cells in inflammatory reactions of the airways, skin and intestine. 1994, Pubmed
Martinez-Palomo, Localization of permeability barriers in the frog skin epithelium. 1971, Pubmed
Matsui, Dissecting the formation, structure and barrier function of the stratum corneum. 2015, Pubmed
Matthijs, Low structural variation in the host-defense peptide repertoire of the dwarf clawed frog Hymenochirus boettgeri (Pipidae). 2014, Pubmed , Xenbase
Matutte, Induction of synthesis of an antimicrobial peptide in the skin of the freeze-tolerant frog, Rana sylvatica, in response to environmental stimuli. 2000, Pubmed
McCoy, Pesticides Could Alter Amphibian Skin Microbiomes and the Effects of Batrachochytrium dendrobatidis. 2018, Pubmed
McKenzie, Co-habiting amphibian species harbor unique skin bacterial communities in wild populations. 2012, Pubmed
Mechkarska, Antimicrobial peptides with therapeutic potential from skin secretions of the Marsabit clawed frog Xenopus borealis (Pipidae). 2010, Pubmed , Xenbase
Mesquita, Low resistance to chytridiomycosis in direct-developing amphibians. 2017, Pubmed
Miele, Involvement of Rel factors in the expression of antimicrobial peptide genes in amphibia. 2001, Pubmed
Mills, Morphology of the exocrine glands of the frog skin. 1984, Pubmed
Minakhina, Nuclear factor-kappa B pathways in Drosophila. 2006, Pubmed
Mor, The vertebrate peptide antibiotics dermaseptins have overlapping structural features but target specific microorganisms. 1994, Pubmed , Xenbase
Mor, Isolation and structure of novel defensive peptides from frog skin. 1994, Pubmed
Morales, Characterization of primary and memory CD8 T-cell responses against ranavirus (FV3) in Xenopus laevis. 2007, Pubmed , Xenbase
Morales, Innate immune responses and permissiveness to ranavirus infection of peritoneal leukocytes in the frog Xenopus laevis. 2010, Pubmed , Xenbase
Munoz, Plakophilin-3 is required for late embryonic amphibian development, exhibiting roles in ectodermal and neural tissues. 2012, Pubmed , Xenbase
Münster, Magainin 2 in phospholipid bilayers: peptide orientation and lipid chain ordering studied by X-ray diffraction. 2002, Pubmed , Xenbase
Myers, Synergistic inhibition of the lethal fungal pathogen Batrachochytrium dendrobatidis: the combined effect of symbiotic bacterial metabolites and antimicrobial peptides of the frog Rana muscosa. 2012, Pubmed
Nedelkovska, Hsp72 mediates stronger antigen-dependent non-classical MHC class Ib anti-tumor responses than hsc73 in Xenopus laevis. 2013, Pubmed , Xenbase
Nedelkovska, Effective RNAi-mediated β2-microglobulin loss of function by transgenesis in Xenopus laevis. 2013, Pubmed , Xenbase
Nikolaeva, Frog urinary bladder epithelial cells express TLR4 and respond to bacterial LPS by increase of iNOS expression and L-arginine uptake. 2012, Pubmed
Niyonsaba, Friends or Foes? Host defense (antimicrobial) peptides and proteins in human skin diseases. 2017, Pubmed
Nizet, Innate antimicrobial peptide protects the skin from invasive bacterial infection. 2001, Pubmed
Nokhbatolfoghahai, Surface ciliation of anuran amphibian larvae: persistence to late stages in some species but not others. 2006, Pubmed
Novales Flamarique, UV-B induced damage to the skin and ocular system of amphibians. 2000, Pubmed
Ohmer, Skin sloughing in susceptible and resistant amphibians regulates infection with a fungal pathogen. 2017, Pubmed
Ojo, Frog skin peptides (tigerinin-1R, magainin-AM1, -AM2, CPF-AM1, and PGla-AM1) stimulate secretion of glucagon-like peptide 1 (GLP-1) by GLUTag cells. 2013, Pubmed , Xenbase
Pelli, Glycosaminoglycans and glycoconjugates in the adult anuran integument (Lithobates catesbeianus). 2010, Pubmed
Pérez-Iglesias, Toxic and genotoxic effects of the imazethapyr-based herbicide formulation Pivot H® on montevideo tree frog Hypsiboas pulchellus tadpoles (Anura, Hylidae). 2015, Pubmed
Pino-Angeles, Pore Structure and Synergy in Antimicrobial Peptides of the Magainin Family. 2016, Pubmed
Plotkowski, Cellular and molecular mechanisms of bacterial adhesion to respiratory mucosa. 1993, Pubmed
Pochini, Reciprocal effects of pesticides and pathogens on amphibian hosts: The importance of exposure order and timing. 2017, Pubmed
Prates, Skin glands, poison and mimicry in dendrobatid and leptodactylid amphibians. 2012, Pubmed
Proksch, The skin: an indispensable barrier. 2008, Pubmed
Qiao, Transcriptome profile of the green odorous frog (Odorrana margaretae). 2013, Pubmed
Quaranta, Why amphibians are more sensitive than mammals to xenobiotics. 2009, Pubmed
Ramanayake, In vivo study of T-cell responses to skin alloantigens in Xenopus using a novel whole-mount immunohistology method. 2007, Pubmed , Xenbase
Ramsey, Immune defenses against Batrachochytrium dendrobatidis, a fungus linked to global amphibian declines, in the South African clawed frog, Xenopus laevis. 2010, Pubmed , Xenbase
Rauta, Toll-like receptors (TLRs) in aquatic animals: signaling pathways, expressions and immune responses. 2014, Pubmed
Rebollar, Direct and Indirect Horizontal Transmission of the Antifungal Probiotic Bacterium Janthinobacterium lividum on Green Frog (Lithobates clamitans) Tadpoles. 2016, Pubmed
Ribet, How bacterial pathogens colonize their hosts and invade deeper tissues. 2015, Pubmed
Roach, The evolution of vertebrate Toll-like receptors. 2005, Pubmed
Robert, Adaptive immunity and histopathology in frog virus 3-infected Xenopus. 2005, Pubmed , Xenbase
Robert, Waterborne infectivity of the Ranavirus frog virus 3 in Xenopus laevis. 2011, Pubmed , Xenbase
Robert, Xenopus laevis: a possible vector of Ranavirus infection? 2007, Pubmed , Xenbase
Robertson, Transcriptome resources for the frogs Lithobates clamitans and Pseudacris regilla, emphasizing antimicrobial peptides and conserved loci for phylogenetics. 2014, Pubmed , Xenbase
Rodrigues Hoffmann, The cutaneous ecosystem: the roles of the skin microbiome in health and its association with inflammatory skin conditions in humans and animals. 2017, Pubmed
Rodríguez, Discovery of skin alkaloids in a miniaturized eleutherodactylid frog from Cuba. 2011, Pubmed
Roelants, Origin and functional diversification of an amphibian defense peptide arsenal. 2013, Pubmed , Xenbase
Rohr, A pesticide paradox: fungicides indirectly increase fungal infections. 2017, Pubmed
Rollins-Smith, Antimicrobial peptide defenses of the mountain yellow-legged frog (Rana muscosa). 2006, Pubmed
Rollins-Smith, Coqui frogs persist with the deadly chytrid fungus despite a lack of defensive antimicrobial peptides. 2015, Pubmed
Rollins-Smith, Antimicrobial peptide defenses against chytridiomycosis, an emerging infectious disease of amphibian populations. 2005, Pubmed
Rollins-Smith, The role of amphibian antimicrobial peptides in protection of amphibians from pathogens linked to global amphibian declines. 2009, Pubmed
Rollins-Smith, Antimicrobial Peptide defenses in amphibian skin. 2005, Pubmed
Rollins-Smith, Antimicrobial peptide defenses against pathogens associated with global amphibian declines. 2002, Pubmed
Rollins-Smith, Antimicrobial peptide defenses of the Tarahumara frog, Rana tarahumarae. 2002, Pubmed
Rosenblum, Only skin deep: shared genetic response to the deadly chytrid fungus in susceptible frog species. 2012, Pubmed , Xenbase
Rota, Skin of the Red Eye Tree Frog Agalychnis Callidryas (Hylidae, Phyllomedusinae) Contains Lipid Glands of the Type Described in the Genus Phyllomedusa. 2017, Pubmed
Sabino-Pinto, Composition of the Cutaneous Bacterial Community in Japanese Amphibians: Effects of Captivity, Host Species, and Body Region. 2016, Pubmed
Saito, Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2. 2007, Pubmed
Savage, Conservation and divergence in the frog immunome: pyrosequencing and de novo assembly of immune tissue transcriptomes. 2014, Pubmed
Schadich, Neutralization of bacterial endotoxins by frog antimicrobial peptides. 2013, Pubmed
Schumacher, Molecular anatomy of a skin gland: histochemical and biochemical investigations on the mucous glands of Xenopus laevis. 1994, Pubmed , Xenbase
Seki, Development of Xenopus laevis skin glands producing 5-hydroxytryptamine and caerulein. 1989, Pubmed , Xenbase
Selsted, Mammalian defensins in the antimicrobial immune response. 2005, Pubmed
Shahin, Demonstration of gap junctions in frog skin epithelium. 1989, Pubmed
Sifkarovski, Negative effects of low dose atrazine exposure on the development of effective immunity to FV3 in Xenopus laevis. 2014, Pubmed , Xenbase
Simmaco, Antimicrobial peptides from skin secretions of Rana esculenta. Molecular cloning of cDNAs encoding esculentin and brevinins and isolation of new active peptides. 1994, Pubmed
Simoncelli, Short-term cadmium exposure induces stress responses in frog (Pelophylax bergeri) skin organ culture. 2015, Pubmed
Sjöberg, Innervation of skin glands in the frog. 1976, Pubmed
Song, The evolution and origin of animal Toll-like receptor signaling pathway revealed by network-level molecular evolutionary analyses. 2012, Pubmed
Sonna, Invited review: Effects of heat and cold stress on mammalian gene expression. 2002, Pubmed
Soravia, Antimicrobial properties of peptides from Xenopus granular gland secretions. 1988, Pubmed , Xenbase
Sousa, Leptoglycin: a new Glycine/Leucine-rich antimicrobial peptide isolated from the skin secretion of the South American frog Leptodactylus pentadactylus (Leptodactylidae). 2009, Pubmed
Sperandio, Mucosal physical and chemical innate barriers: Lessons from microbial evasion strategies. 2015, Pubmed
Stannard, Ciliary function and the role of cilia in clearance. 2006, Pubmed
Steinman, An electron microscopic study of ciliogenesis in developing epidermis and trachea in the embryo of Xenopus laevis. 1968, Pubmed , Xenbase
Stuart, Status and trends of amphibian declines and extinctions worldwide. 2004, Pubmed
Suhrbier, An investigation of the molecular components of desmosomes in epithelial cells of five vertebrates. 1986, Pubmed
Suzuki, Amphibian aquaporins and adaptation to terrestrial environments: a review. 2007, Pubmed
Talbott, Factors influencing detection and co-detection of Ranavirus and Batrachochytrium dendrobatidis in Midwestern North American anuran populations. 2018, Pubmed
Tennessen, Traffic noise causes physiological stress and impairs breeding migration behaviour in frogs. 2014, Pubmed
Thwaite, The cationic peptide magainin II is antimicrobial for Burkholderia cepacia-complex strains. 2009, Pubmed , Xenbase
van Dijk, Immunomodulatory and Anti-Inflammatory Activities of Chicken Cathelicidin-2 Derived Peptides. 2016, Pubmed
Van Meter, Estimating terrestrial amphibian pesticide body burden through dermal exposure. 2014, Pubmed
Wada, Helicobacter pylori-mediated transcriptional regulation of the human beta-defensin 2 gene requires NF-kappaB. 2001, Pubmed
Walentek, A novel serotonin-secreting cell type regulates ciliary motility in the mucociliary epidermis of Xenopus tadpoles. 2014, Pubmed , Xenbase
Walke, Harnessing the Microbiome to Prevent Fungal Infections: Lessons from Amphibians. 2016, Pubmed
Walke, Most of the Dominant Members of Amphibian Skin Bacterial Communities Can Be Readily Cultured. 2015, Pubmed
Wang, APD3: the antimicrobial peptide database as a tool for research and education. 2016, Pubmed
Wang, Selection and environmental adaptation along a path to speciation in the Tibetan frog Nanorana parkeri. 2018, Pubmed
Warner, The role of gap junctions in amphibian development. 1985, Pubmed , Xenbase
Wendel, Amphibian (Xenopus laevis) tadpoles and adult frogs mount distinct interferon responses to the Frog Virus 3 ranavirus. 2017, Pubmed , Xenbase
Wendel, Amphibian (Xenopus laevis) Tadpoles and Adult Frogs Differ in Their Use of Expanded Repertoires of Type I and Type III Interferon Cytokines. 2018, Pubmed , Xenbase
Woodhams, Life history linked to immune investment in developing amphibians. 2016, Pubmed
Wu, A frog cathelicidin peptide effectively promotes cutaneous wound healing in mice. 2018, Pubmed
Wullaert, NF-κB in the regulation of epithelial homeostasis and inflammation. 2011, Pubmed
Xi, Expressions of IL-6, TNF-α and NF-κB in the skin of Chinese brown frog (Rana dybowskii). 2017, Pubmed
Xiao, Analysis of skin and secretions of Dybowski's frogs (Rana dybowskii) exposed to Staphylococcus aureus or Escherichia coli identifies immune response proteins. 2014, Pubmed
Yamasaki, Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. 2007, Pubmed
Yang, NF-kappaB factors are essential, but not the switch, for pathogen-related induction of the bovine beta-defensin 5-encoding gene in mammary epithelial cells. 2006, Pubmed
Yokoyama, Skin regeneration of amphibians: A novel model for skin regeneration as adults. 2018, Pubmed , Xenbase
Yu, Joint effects of pesticides and ultraviolet-B radiation on amphibian larvae. 2015, Pubmed , Xenbase
Zasloff, Magainins, a class of antimicrobial peptides from Xenopus skin: isolation, characterization of two active forms, and partial cDNA sequence of a precursor. 1987, Pubmed , Xenbase
Zasloff, Antimicrobial peptides of multicellular organisms. 2002, Pubmed
Zasloff, Antibiotic peptides as mediators of innate immunity. 1992, Pubmed , Xenbase
Zhang, Transcriptome analysis and identification of genes related to immune function in skin of the Chinese brown frog. 2009, Pubmed , Xenbase
Zhao, Comprehensive transcriptome profiling and functional analysis of the frog (Bombina maxima) immune system. 2014, Pubmed
Zou, Origin and evolution of the RIG-I like RNA helicase gene family. 2009, Pubmed