scholarly journals Selective constraint acting on TLR2 and TLR4 genes of Japanese Rana frogs

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4842 ◽  
Author(s):  
Quintin Lau ◽  
Takeshi Igawa ◽  
Tiffany A. Kosch ◽  
Yoko Satta

Toll-like receptors (TLRs) are an important component of innate immunity, the first line of pathogen defence. One of the major roles of TLRs includes recognition of pathogen-associated molecular patterns. Amphibians are currently facing population declines and even extinction due to chytridiomycosis caused by the Batrachochytrium dendrobatidis (Bd) fungus. Evidence from other vertebrates shows that TLR2 and TLR4 are involved in innate immunity against various fungi. Such genes therefore may play a functional role in amphibian-chytridiomycosis dynamics. Frogs from East Asia appear to be tolerant to Bd, so we examined the genetic diversity that underlies TLR2 and TLR4 from three Japanese Ranidae frog species, Rana japonica, R. ornativentris and R. tagoi tagoi (n = 5 per species). We isolated 27 TLR2 and 20 TLR4 alleles and found that these genes are evolutionarily conserved, with overall evidence supporting purifying selection. In contrast, site-by-site analysis of selection identified several specific codon sites under positive selection, some of which were located in the variable leucine rich repeat domains. In addition, preliminary expression levels of TLR2 and TLR4 from transcriptome data showed overall low expression. Although it remains unclear whether infectious pathogens are a selective force acting on TLRs of Japanese frogs, our results support that certain sites in TLRs of these species may have experienced pathogen-mediated selection.


2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Federica Moalli ◽  
Sebastien Jaillon ◽  
Antonio Inforzato ◽  
Marina Sironi ◽  
Barbara Bottazzi ◽  
...  

Innate immunity represents the first line of defence against pathogens and plays key roles in activation and orientation of the adaptive immune response. The innate immune system comprises both a cellular and a humoral arm. Components of the humoral arm include soluble pattern recognition molecules (PRMs) that recognise pathogen-associated molecular patterns (PAMPs) and initiate the immune response in coordination with the cellular arm, therefore acting as functional ancestors of antibodies. The long pentraxin PTX3 is a prototypic soluble PRM that is produced at sites of infection and inflammation by both somatic and immune cells. Gene targeting of this evolutionarily conserved protein has revealed a nonredundant role in resistance to selected pathogens. Moreover, PTX3 exerts important functions at the cross-road between innate immunity, inflammation, and female fertility. Here, we review the studies on PTX3, with emphasis on pathogen recognition and cross-talk with other components of the innate immune system.



Author(s):  
Andrea Costa ◽  
Lorenzo Dondero ◽  
Giorgia Allaria ◽  
Bryan Nelson Morales Sanchez ◽  
Giacomo Rosa ◽  
...  

AbstractThe emerging amphibian disease, Batrachochytrium dendrobatidis (Bd), is driving population declines worldwide and even species extinctions in Australia, South and Central America. In order to mitigate effects of Bd on amphibian populations, high-exposed areas should be identified at the local scale and effective conservation measures should be planned at the national level. This assessment is actually lacking in the Mediterranean basin, and in particular in Italy, one of the most relevant amphibian diversity hotspots in the entire region. In this study, we reviewed the available information on Bd in Italy, and conducted a 5-year molecular screening on 1274 individual skin swabs belonging to 18 species. Overall, we found presence of Bd in 13 species and in a total of 56 known occurrence locations for peninsular Italy and Sardinia. We used these occurrence locations and climate data to model habitat suitability of Bd for current and future climatic scenarios. We then employed electric circuit theory to model landscape permeability to the diffusion of Bd, using a resistance map. With this procedure, we were able to model, for the first time, the diffusion pathways of Bd at the landscape scale, characterising the main future pathways towards areas with a high probability of Bd occurrence. Thus, we identified six national protected areas that will become pivotal for a nationally-based strategic plan in order to monitor, mitigate and possibly contrast Bd diffusion in Italy.



2021 ◽  
Vol 57 (4) ◽  
Author(s):  
David A. Narváez-Narváez ◽  
Alejandro Cabrera-Andrade ◽  
Andrés Merino-Viteri ◽  
César Paz-y-Miño ◽  
Germán Burgos ◽  
...  


PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2079 ◽  
Author(s):  
Jinlan Wang ◽  
Zheng Zhang ◽  
Fen Chang ◽  
Deling Yin

Toll-like receptors (TLRs) play important role in the innate immune system. TLR15 is reported to have a unique role in defense against pathogens, but its structural and evolution characterizations are still poorly understood. In this study, we identified 57 completed TLR15 genes from avian and reptilian genomes. TLR15 clustered into an individual clade and was closely related to family 1 on the phylogenetic tree. Unlike the TLRs in family 1 with the broken asparagine ladders in the middle, TLR15 ectodomain had an intact asparagine ladder that is critical to maintain the overall shape of ectodomain. The conservation analysis found that TLR15 ectodomain had a highly evolutionarily conserved region on the convex surface of LRR11 module, which is probably involved in TLR15 activation process. Furthermore, the protein–protein docking analysis indicated that TLR15 TIR domains have the potential to form homodimers, the predicted interaction interface of TIR dimer was formed mainly by residues from the BB-loops andαC-helixes. Although TLR15 mainly underwent purifying selection, we detected 27 sites under positive selection for TLR15, 24 of which are located on its ectodomain. Our observations suggest the structural features of TLR15 which may be relevant to its function, but which requires further experimental validation.



Author(s):  
О.Ю. Филатов ◽  
В.А. Назаров

Данная статья обобщает накопившуюся на сегодняшний день информацию о многообразии образраспознающих рецепторов, их роли в регуляции иммунной системы. Распознавание патогена врожденным иммунитетом происходит с помощью рецепторов к широкому спектру антигенов за счет выделения нескольких высоко консервативных структур микроорганизмов. Эти структуры были названы патоген-ассоциированные образы (Patogen-Associated Molecular Patterns - PAMP). Наиболее изученными являются липополисахарид грамм отрицательных бактерий (LPS), липотейхоевые кислоты, пептидогликан (PGN), CpG мотивы ДНК и РНК. Рецепторы, распознающие PAMP, называются PRR. Данная группа рецепторов также распознает молекулы, образующиеся при повреждении собственных тканей. Такие молекулярные структуры называются Damage-Associated Molecular Patterns (DAMP), или образы, ассоциированные с повреждением. В качестве DAMP могут выступать белки теплового шока, хроматин, фрагменты ДНК. В зависимости от локализации, образраспознающие рецепторы принято разделять на: расположенные на мембране Toll-подобные рецепторы (Toll-like receptors, TLR) и рецепторы лектина С-типа (C-type lectin receptors, CLR), а также расположенные в цитоплазме NOD-подобные рецепторы (NOD-like receptors, NLR) и цитоплазматические РНК- и ДНК-сенсоры. Сегодня у человека известно 10 типов TLR, часть из которых расположена на поверхности (TLR1-TLR6, TLR10) большинства клеток, в том числе макрофагов, В-лимфоцитов и дендритных клеток, а часть - в эндосомах (TLR3, TLR7-TLR9). CLR представляет из себя семейство рецепторов, расположенных на мембране и имеющих домены распознавания углеводов (CRD), или структурно сходные лектиноподобные домены типа C (CTLD). В данном семействе рецепторов принято по происхождению и структуре выделять 17 групп. CLR активно участвуют в противогрибковой иммунной защите, а также они играют роль в защите и от других типов микроорганизмов. NOD (нуклеотидсвязывающий и олигомеризационный домен)-подобные рецепторы расположены в цитоплазме. Благодаря этим рецепторам, патоген, который избежал распознавания на поверхности мембраны, сталкивается со вторым уровнем распознавания уже внутри клетки. В данной статье рассматриваются пути активации образраспознающих рецепторов, их эффекты и применение данных эффектов в медицине. This article summarizes currently available information about the variety of image-recognizing receptors and their role in regulation of the immune system. Pathogen recognition by the innate immunity is mediated by receptors to a wide range of antigens via recognition of several highly conservative structures of microorganisms. These structures were named pathogen-associated images or PAMP (pathogen-associated molecular pattern). The best studied types of such structures include lipopolysaccharide (LPS) of gram-negative bacteria, lipoteichoic acids, peptidoglycan (PGN), and CpG DNA and RNA motifs. PAMP-recognizing receptors (PRRS) are a group of receptors, which also recognize molecules released during damage of host tissues. Such molecular structures are called DAMPS (damage-associated molecular patterns) or damage-associated images. Heat shock proteins, chromatin, and DNA fragments may act as DAMPS. Depending on the localization, image-recognizing receptors are generally classified as membrane-located Toll-like receptors (TLR) and C-type lectin receptors (CLR), as well as cytoplasmic NOD-like receptors (NLR) and cytoplasmic RNA and DNA sensors. Today, 10 types of human TLR are known. Some of them are located on the surface (TLR1-TLR6, TLR10) of most cells, including macrophages, B-cells, and dendritic cells, and some are present in endosomes (TLR3, TLR7-TLR9). CLR is a family of membrane receptors that have carbohydrate recognition domains (CRD) or structurally similar lectin-like type C domains (CTLD). Seventeen groups are distinguished within this receptor family based on their origin and structure. CLRs are actively involved in antifungal immune defense and also play a role in protection against other types of microorganisms. NOD (nucleotide-binding and oligomerization domain)-like receptors are present in the cytoplasm. These receptors provide the second level of recognition inside the cell for the pathogens that have escaped recognition on the membrane surface. This article discusses activation pathways of image-recognizing receptors, their effects, and the use of such effects in medicine.



Author(s):  
Anat Belasen ◽  
Kevin Amses ◽  
Rebecca Clemons ◽  
Guilherme Becker ◽  
Felipe Toledo ◽  
...  

Habitat fragmentation and infectious disease threaten amphibians globally, but little is known about how these two threats interact. In this study, we examined the effects of Brazilian Atlantic Forest habitat fragmentation on frog genetic diversity at an immune locus known to affect disease susceptibility in amphibians, the MHC IIB locus. We used a custom high-throughput assay to sequence the MHC IIB locus across six focal frog species in two regions of the Atlantic Forest. We also used a molecular assay to quantify infections by the fungal pathogen Batrachochytrium dendrobatidis (Bd). We found that habitat fragmentation is associated with genetic erosion at the MHC IIB locus, and that this erosion is most severe in frog species restricted to intact forests. Significant Bd infections were recovered only in one Atlantic Forest region, potentially due to the relatively higher elevation. In this region, forest specialists showed an increase in both Bd prevalence and loads in fragmented habitats. We also found that reduced population-level MHC IIB diversity was associated with increased Bd infection risk. On the individual-level, MHC IIB heterozygotes (by allelic genotype as well as supertype) exhibited a reduced risk of Bd infection. Our results suggest that habitat fragmentation increases infection susceptibility in amphibians, mediated at least in part through loss of immunogenetic diversity. Our findings have implications for the conservation of fragmented populations in the face of emerging infectious diseases.



Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Göran K. Hansson

Immune responses participate in every phase of atherosclerosis. Indeed, atherosclerosis can be viewed as an immune/inflammatory response to lipoprotein retention in the artery wall. There is increasing evidence that both adaptive and innate immunity tightly regulate the atherosclerotic process. Specific antigens and pathogen-like molecular patterns initiate the 2 aspects of immunity by ligating T- and B-cell receptors and pattern recognition receptors, respectively. Effector responses of vascular immune reactions include macrophage activation, cellular immunity, antibody formation, and vascular inflammation. Whereas experimental studies in gene-targeted models have identified major roles for innate immunity and Th1 responses in plaque initiation and progression, clinical, epidemiological and genetic studies suggest that plaque activation, rupture, and atherothrombosis also depend on immune reactions. This lecture will focus on the role of immune mechanisms in the formation and activation of atherosclerotic plaques.



2019 ◽  
Vol 286 (1904) ◽  
pp. 20190833 ◽  
Author(s):  
Minjie Fu ◽  
Bruce Waldman

Many amphibian species around the world, except in Asia, suffer morbidity and mortality when infected by the emerging infectious pathogen Batrachochytrium dendrobatidis (Bd). A lineage of the amphibian chytrid fungus isolated from South Korean amphibians (BdAsia-1) is evolutionarily basal to recombinant global pandemic lineages (BdGPL) associated with worldwide amphibian population declines. In Asia, the Bd pathogen and its amphibian hosts have coevolved over 100 years or more. Thus, resilience of Asian amphibian populations to infection might result from attenuated virulence of endemic Bd lineages, evolved immunity to the pathogen or both. We compared susceptibilities of an Australasian amphibian, Litoria caerulea , known to lack resistance to BdGPL, with those of three Korean species, Bufo gargarizans , Bombina orientalis and Hyla japonica , after inoculation with BdAsia-1, BdGPL or a blank solution. Subjects became infected in all experimental treatments but Korean species rapidly cleared themselves of infection, regardless of Bd lineage. They survived with no apparent secondary effects. By contrast, L. caerulea , after infection by either BdAsia-1 or BdGPL, suffered deteriorating body condition and carried progressively higher Bd loads over time. Subsequently, most subjects died. Comparing their effects on L. caerulea , BdAsia-1 induced more rapid disease progression than BdGPL. The results suggest that genomic recombination with other lineages was not necessary for the ancestral Bd lineage to evolve hypervirulence over its long period of coevolution with amphibian hosts. The pathogen's virulence may have driven strong selection for immune responses in endemic Asian amphibian host species.



2019 ◽  
Vol 31 (2) ◽  
pp. 246-249 ◽  
Author(s):  
Claudio Borteiro ◽  
Francisco Kolenc ◽  
José Manuel Verdes ◽  
Claudio Martínez Debat ◽  
Martín Ubilla

Histology is often underappreciated for the detection of the amphibian pathogenic fungus Batrachochytrium dendrobatidis, the cause of the potentially lethal skin disease chytridiomycosis. We evaluated the sensitivity of histology to detect chytrids in 20 wild specimens of 2 frog species from Uruguay that were clinically normal, but confirmed by PCR to be infected by B. dendrobatidis. We detected maturing and sporulated sporangia in 15 of 20 (75%) frogs, which is more sensitive than previously reported for histology. The effort needed to identify chytrids in histologic skin sections of Physalaemus henselii and Pleurodema bibroni required examination of 3.2 and 8.7 mm of skin sections for each frog species, respectively.



2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Eugene J. Gardner ◽  
Elena Prigmore ◽  
Giuseppe Gallone ◽  
Petr Danecek ◽  
Kaitlin E. Samocha ◽  
...  

Abstract Mobile genetic Elements (MEs) are segments of DNA which can copy themselves and other transcribed sequences through the process of retrotransposition (RT). In humans several disorders have been attributed to RT, but the role of RT in severe developmental disorders (DD) has not yet been explored. Here we identify RT-derived events in 9738 exome sequenced trios with DD-affected probands. We ascertain 9 de novo MEs, 4 of which are likely causative of the patient’s symptoms (0.04%), as well as 2 de novo gene retroduplications. Beyond identifying likely diagnostic RT events, we estimate genome-wide germline ME mutation rate and selective constraint and demonstrate that coding RT events have signatures of purifying selection equivalent to those of truncating mutations. Overall, our analysis represents a comprehensive interrogation of the impact of retrotransposition on protein coding genes and a framework for future evolutionary and disease studies.



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