The genes of major histocompatibility complex (MHC) provide an excellent opportunity to study host-parasite relationships because they are expected to evolve in response to parasites and variation in parasite communities. In this study, we investigated the potential role of parasite-mediated selection acting on MHC class IIB (DAB) genes in European chub (Squalius cephalus) natural populations. We found significant differences between populations in metazoan parasites, neutral and adaptive genetic diversities. The analyses based on pairwise data revealed that populations with dissimilar MHC allelic profiles were geographically distant populations with significantly different diversity in microsatellites and a dissimilar composition of parasite communities. The results from the generalized estimating equations method (GEE) on the level of individuals revealed that metazoan parasite load in European chub was influenced by the diversity of DAB alleles as well as by the diversity of neutral genetic markers and host traits reflecting condition and immunocompetence. The multivariate co-inertia analysis showed specific associations between DAB alleles and parasite species. DAB1-like alleles were more involved in associations with ectoparasites, while DAB3-like alleles were positively associated with endoparasites which could suggest potential differences between DAB genes caused by different selection pressure. Our study revealed that parasite-mediated selection is not the only variable affecting MHC diversity in European chub; however, we strongly support the role of neutral processes as the main driver of DAB diversity across populations. In addition, our study contributes to the understanding of the evolution of MHC genes in wild living fish.

• MeSH
• alely MeSH
• Cyprinidae genetika   MeSH
• divoká zvířata MeSH
• genetická variace * MeSH
• hlavní histokompatibilní komplex genetika   MeSH
• interakce hostitele a parazita MeSH
• mikrosatelitní repetice genetika   MeSH
• nemoci ryb parazitologie   MeSH
• parazitární nemoci u zvířat epidemiologie   genetika   parazitologie   MeSH
• paraziti MeSH
• selekce (genetika) * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH

The ectoparasitic mite Varroa destructor transmits and triggers viral infections that have deleterious effects on honey bee colonies worldwide. We performed a manipulative experiment in which worker bees collected at emergence were exposed to Varroa for 72 h, and their proteomes were compared with those of untreated control bees. Label-free quantitative proteomics identified 77 differentially expressed A. mellifera proteins (DEPs). In addition, viral proteins were identified by orthogonal analysis, and most importantly, Deformed wing virus (DWV) was found at high levels/intensity in Varroa-exposed bees. Pathway enrichment analysis suggested that the main pathways affected included peroxisomal metabolism, cyto-/exoskeleton reorganization, and cuticular proteins. Detailed examination of individual DEPs revealed that additional changes in DEPs were associated with peroxisomal function. In addition, the proteome data support the importance of TGF-β signaling in Varroa-DWV interaction and the involvement of the mTORC1 and Hippo pathways. These results suggest that the effect of DWV on bees associated with Varroa feeding results in aberrant autophagy. In particular, autophagy is selectively modulated by peroxisomes, to which the observed proteome changes strongly corresponded. This study complements previous research with different study designs and suggests the importance of the peroxisome, which plays a key role in viral infections.

• MeSH
• hmyzí proteiny metabolismus   MeSH
• interakce hostitele a parazita MeSH
• peroxizomy * metabolismus   virologie   MeSH
• proteom metabolismus   analýza   MeSH
• proteomika metody   MeSH
• RNA-viry * fyziologie   MeSH
• signální transdukce MeSH
• Varroidae * virologie   MeSH
• včely virologie   parazitologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Sedentary plant-parasitic cyst nematodes are biotrophs that cause significant losses in agriculture. Parasitism is based on modifications of host root cells that lead to the formation of a hypermetabolic feeding site (a syncytium) from which nematodes withdraw nutrients. The host cell cycle is activated in an initial cell selected by the nematode for feeding, followed by activation of neighboring cells and subsequent expansion of feeding site through fusion of hundreds of cells. It is generally assumed that nematodes manipulate production and signaling of the plant hormone cytokinin to activate cell division. In fact, nematodes have been shown to produce cytokinin in vitro; however, whether the hormone is secreted into host plants and plays a role in parasitism remained unknown. Here, we analyzed the spatiotemporal activation of cytokinin signaling during interaction between the cyst nematode, Heterodera schachtii, and Arabidopsis using cytokinin-responsive promoter:reporter lines. Our results showed that cytokinin signaling is activated not only in the syncytium but also in neighboring cells to be incorporated into syncytium. An analysis of nematode infection on mutants that are deficient in cytokinin or cytokinin signaling revealed a significant decrease in susceptibility of these plants to nematodes. Further, we identified a cytokinin-synthesizing isopentenyltransferase gene in H. schachtii and show that silencing of this gene in nematodes leads to a significant decrease in virulence due to a reduced expansion of feeding sites. Our findings demonstrate the ability of a plant-parasitic nematode to synthesize a functional plant hormone to manipulate the host system and establish a long-term parasitic interaction.

• MeSH
• Arabidopsis * genetika   metabolismus   parazitologie   MeSH
• cytokininy genetika   metabolismus   MeSH
• hlístice fyziologie   MeSH
• interakce hostitele a parazita fyziologie   MeSH
• molekulární sekvence - údaje MeSH
• nemoci rostlin parazitologie   MeSH
• sekvence nukleotidů MeSH
• signální transdukce * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

BACKGROUND: The gibel carp is a fish species with dual reproduction modes, gynogenesis and sexual reproduction, coexisting in mixed diploid-polyploid populations. Following the Red Queen (RQ) assumption, asexual organisms are, due to their low genetic diversity, targets for parasite adaptation. Because MHC polymorphism is maintained by selection from parasites and sexual selection, MHC genes are considered as a suitable candidate for testing the RQ hypothesis. In this study, we investigated MHC variability and the selection pressure acting on MHC genes in sexual diploids and asexual triploids. In addition, we tested whether the asexual form of gibel carp suffers from higher parasite loads than the sexual form. RESULTS: At the population level, genotype and allelic diversity of MHC were reduced in gynogenetic triploids when compared to sexual diploids. Different patterns in positively selected sites (PSS) between gynogens and sexual gibel carp were also found. A weak difference in parasite species richness was found between sexual fish and gynogens. However, two common clones of gynogens were significantly more parasitized than sexual diploids or other gynogens with rare MHC genotypes. At the individual level, the higher number of alleles was not associated with higher parasitism in either sexual diploids or gynogens. CONCLUSIONS: The differences in MHC diversity between gynogenetic triploids and sexual diploids are in accordance with the hypothesis of sexually-mediated selection increasing MHC diversity and fulfil a prerequisite of the Red Queen hypothesis. The different patterns in PSS between gynogens and sexual gibel carp also suggest the potential role of sexual selection and supports parasite-mediated selection maintaining MHC diversity. We showed that the most common MHC genotypes of gynogenetic triploids are the target of parasite selection. Our results suggest that the MHC genotype in gibel carp is more important than allelic number for immunocompetence.

• MeSH
• diploidie * MeSH
• genetická variace MeSH
• genotyp MeSH
• hlavní histokompatibilní komplex * MeSH
• kapři genetika   fyziologie   MeSH
• rozmnožování * MeSH
• rybí proteiny genetika   MeSH
• triploidie * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• alergologie a imunologie MeSH
• imunitní systém MeSH
• infekční nemoci imunologie   MeSH
• nádory imunologie   MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• alergologie a imunologie
• infekční lékařství
• NLK Publikační typ
• učebnice vysokých škol

Immune genes show remarkable levels of adaptive variation shaped by pathogen-mediated selection. Compared to humans, however, population polymorphism in animals has been understudied. To provide an insight into immunogenetic diversity in birds, we sequenced complete protein-coding regions of all Toll-like receptor (TLR) genes with direct orthology between mammals and birds (TLR3, TLR4, TLR5 and TLR7) in 110 domestic chickens from 25 breeds and compared their variability with a corresponding human dataset. Chicken TLRs (chTLRs) exhibit on average nine-times higher nucleotide diversity than human TLRs (hTLRs). Increased potentially functional non-synonymous variability is found in chTLR ligand-binding ectodomains. While we identified seven sites in chTLRs under positive selection and found evidence for convergence between alleles, no selection or convergence was detected in hTLRs. Up to six-times more alleles were identified in fowl (70 chTLR4 alleles vs. 11 hTLR4 alleles). In chTLRs, high numbers of alleles are shared between the breeds and the allelic frequencies are more equal than in hTLRs. These differences may have an important impact on infectious disease resistance and host-parasite co-evolution. Though adaptation through high genetic variation is typical for acquired immunity (e.g. MHC), our results show striking levels of intraspecific polymorphism also in poultry innate immune receptors.

• MeSH
• frekvence genu MeSH
• genetická variace * MeSH
• kur domácí * MeSH
• lidé MeSH
• sekvenční analýza DNA MeSH
• toll-like receptory genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• alergologie a imunologie

The leishmaniases are globally important parasitic diseases for which no human vaccines are currently available. To facilitate vaccine development, we conducted an open-label observational study to establish a controlled human infection model (CHIM) of sand fly-transmitted cutaneous leishmaniasis (CL) caused by Leishmania major. Between 24 January and 12 August 2022, we exposed 14 participants to L. major-infected Phlebotomus duboscqi. The primary objective was to demonstrate effectiveness of lesion development (take rate) and safety (absence of CL lesion at 12 months). Secondary and exploratory objectives included rate of lesion development, parasite load and analysis of local immune responses by immunohistology and spatial transcriptomics. Lesion development was terminated by therapeutic biopsy (between days 14 and 42 after bite) in ten participants with clinically compatible lesions, one of which was not confirmed by parasite detection. We estimated an overall take rate for CL development of 64% (9/14). Two of ten participants had one and one of ten participants had two lesion recurrences 4-8 months after biopsy that were treated successfully with cryotherapy. No severe or serious adverse events were recorded, but as expected, scarring due to a combination of CL and the biopsy procedure was evident. All participants were lesion free at >12-month follow-up. We provide the first comprehensive map of immune cell distribution and cytokine/chemokine expression in human CL lesions, revealing discrete immune niches. This CHIM offers opportunities for vaccine candidate selection based on human efficacy data and for a greater understanding of immune-mediated pathology. ClinicalTrials.gov identifier: NCT04512742 .

• MeSH
• dospělí MeSH
• Leishmania major * imunologie   MeSH
• leishmanióza kožní * imunologie   parazitologie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• parazitární zátěž MeSH
• Phlebotomus parazitologie   imunologie   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

INTRODUCTION: Parasite-mediated selection is considered one of the potential mechanisms contributing to the coexistence of asexual-sexual complexes. Gibel carp (Carassius gibelio), an invasive fish species in Europe, often forms populations composed of gynogenetic and sexual specimens. METHODS: The experimental infection was induced in gynogenetic and sexual gibel carp using eye-fluke Diplostomum pseudospathaceum (Trematoda), and the transcriptome profile of the spleen as a major immune organ in fish was analyzed to reveal the differentially expressed immunity-associated genes related to D. pseudospathaceum infection differing between gynogenetic and sexual gibel carp. RESULTS: High parasite infection was found in gynogenetic fish when compared to genetically diverse sexuals. Although metacercariae of D. pseudospathaceum are situated in an immune-privileged organ, our results show that eye trematodes may induce a host immune response. We found differential gene expression induced by eye-fluke infection, with various impacts on gynogenetic and sexual hosts, documenting for the majority of DEGs upregulation in sexuals, and downregulation in asexuals. Differences in gene regulation between gynogenetic and sexual gibel carp were evidenced in many immunity-associated genes. GO analyses revealed the importance of genes assigned to the GO terms: immune function, the Notch signaling pathway, MAP kinase tyrosine/threonine/phosphatase activity, and chemokine receptor activity. KEGG analyses revealed the importance of the genes involved in 12 immunity-associated pathways - specifically, FoxO signaling, adipocytokine signaling, TGF-beta signaling, apoptosis, Notch signaling, C-type lectin receptor signaling, efferocytosis, intestinal immune network for IgA production, insulin signaling, virion - human immunodeficiency virus, Toll-like receptor signaling, and phosphatidylinositol signaling system. DISCUSSION: Our study indicates the limited potential of asexual fish to cope with higher parasite infection (likely a loss of capacity to induce an effective immune response) and highlights the important role of molecular mechanisms associated with immunity for the coexistence of gynogenetic and sexual gibel carp, potentially contributing to its invasiveness.

• MeSH
• infekce červy třídy Trematoda * veterinární   imunologie   parazitologie   MeSH
• interakce hostitele a parazita imunologie   MeSH
• kapři parazitologie   imunologie   genetika   MeSH
• nemoci ryb * imunologie   parazitologie   MeSH
• regulace genové exprese MeSH
• rozmnožování imunologie   MeSH
• stanovení celkové genové exprese MeSH
• transkriptom MeSH
• Trematoda * fyziologie   MeSH
• zavlečené druhy * MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: In vertebrates, it has been repeatedly demonstrated that genes encoding proteins involved in pathogen-recognition by adaptive immunity (e.g. MHC) are subject to intensive diversifying selection. On the other hand, the role and the type of selection processes shaping the evolution of innate-immunity genes are currently far less clear. In this study we analysed the natural variation and the evolutionary processes acting on two genes involved in the innate-immunity recognition of Microbe-Associated Molecular Patterns (MAMPs). RESULTS: We sequenced genes encoding Toll-like receptor 4 (Tlr4) and 7 (Tlr7), two of the key bacterial- and viral-sensing receptors of innate immunity, across 23 species within the subfamily Murinae. Although we have shown that the phylogeny of both Tlr genes is largely congruent with the phylogeny of rodents based on a comparably sized non-immune sequence dataset, we also identified several potentially important discrepancies. The sequence analyses revealed that major parts of both Tlrs are evolving under strong purifying selection, likely due to functional constraints. Yet, also several signatures of positive selection have been found in both genes, with more intense signal in the bacterial-sensing Tlr4 than in the viral-sensing Tlr7. 92% and 100% of sites evolving under positive selection in Tlr4 and Tlr7, respectively, were located in the extracellular domain. Directly in the Ligand-Binding Region (LBR) of TLR4 we identified two rapidly evolving amino acid residues and one site under positive selection, all three likely involved in species-specific recognition of lipopolysaccharide of gram-negative bacteria. In contrast, all putative sites of LBRTLR7 involved in the detection of viral nucleic acids were highly conserved across rodents. Interspecific differences in the predicted 3D-structure of the LBR of both Tlrs were not related to phylogenetic history, while analyses of protein charges clearly discriminated Rattini and Murini clades. CONCLUSIONS: In consequence of the constraints given by the receptor protein function purifying selection has been a dominant force in evolution of Tlrs. Nevertheless, our results show that episodic diversifying parasite-mediated selection has shaped the present species-specific variability in rodent Tlrs. The intensity of diversifying selection was higher in Tlr4 than in Tlr7, presumably due to structural properties of their ligands.

• MeSH
• druhová specificita MeSH
• fylogeneze MeSH
• molekulární evoluce * MeSH
• Murinae klasifikace   genetika   imunologie   MeSH
• přirozená imunita MeSH
• terciární struktura proteinů MeSH
• toll-like receptor 4 chemie   genetika   imunologie   MeSH
• toll-like receptor 7 chemie   genetika   imunologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH