scholarly journals Immunomodulatory Proteins in Tick Saliva From a Structural Perspective

2021 ◽  
Vol 11 ◽  
Author(s):  
Stepan S. Denisov ◽  
Ingrid Dijkgraaf
Keyword(s):  
Immune System ◽  
Gene Duplication ◽  
Defense Mechanisms ◽  
Tick Saliva ◽  
Structure Activity ◽  
Blood Sucking ◽  
Host Relationships ◽  
Related Proteins ◽  
New Vaccines ◽  
Complement Pathways

To feed successfully, ticks must bypass or suppress the host’s defense mechanisms, particularly the immune system. To accomplish this, ticks secrete specialized immunomodulatory proteins into their saliva, just like many other blood-sucking parasites. However, the strategy of ticks is rather unique compared to their counterparts. Ticks’ tendency for gene duplication has led to a diverse arsenal of dozens of closely related proteins from several classes to modulate the immune system’s response. Among these are chemokine-binding proteins, complement pathways inhibitors, ion channels modulators, and numerous poorly characterized proteins whose functions are yet to be uncovered. Studying tick immunomodulatory proteins would not only help to elucidate tick-host relationships but would also provide a rich pool of potential candidates for the development of immunomodulatory intervention drugs and potentially new vaccines. In the present review, we will attempt to summarize novel findings on the salivary immunomodulatory proteins of ticks, focusing on biomolecular targets, structure-activity relationships, and the perspective of their development into therapeutics.

scholarly journals NMR-Based Structural Characterization of a Two-Disulfide-Bonded Analogue of the FXIIIa Inhibitor Tridegin: New Insights into Structure–Activity Relationships

2021 ◽  
Vol 22 (2) ◽  
pp. 880
Author(s):  
Thomas Schmitz ◽  
Ajay Abisheck Paul George ◽  
Britta Nubbemeyer ◽  
Charlotte A. Bäuml ◽  
Torsten Steinmetzer ◽  
...  
Keyword(s):  
Structural Information ◽  
Coagulation Factor ◽  
Md Simulations ◽  
2D Nmr ◽  
Label Free ◽  
2D Nmr Spectroscopy ◽  
Structure Information ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Blood Sucking

The saliva of blood-sucking leeches contains a plethora of anticoagulant substances. One of these compounds derived from Haementeria ghilianii, the 66mer three-disulfide-bonded peptide tridegin, specifically inhibits the blood coagulation factor FXIIIa. Tridegin represents a potential tool for antithrombotic and thrombolytic therapy. We recently synthesized two-disulfide-bonded tridegin variants, which retained their inhibitory potential. For further lead optimization, however, structure information is required. We thus analyzed the structure of a two-disulfide-bonded tridegin isomer by solution 2D NMR spectroscopy in a combinatory approach with subsequent MD simulations. The isomer was studied using two fragments, i.e., the disulfide-bonded N-terminal (Lys1–Cys37) and the flexible C-terminal part (Arg38–Glu66), which allowed for a simplified, label-free NMR-structure elucidation of the 66mer peptide. The structural information was subsequently used in molecular modeling and docking studies to provide insights into the structure–activity relationships. The present study will prospectively support the development of anticoagulant-therapy-relevant compounds targeting FXIIIa.

scholarly journals A Faster and a Stronger Defense Response: One of the Key Elements in Grapevine Explaining Its Lower Level of Susceptibility to Esca?

2013 ◽  
Vol 103 (10) ◽  
pp. 1028-1034 ◽  
Author(s):  
Carole Lambert ◽  
Ian Li Kim Khiook ◽  
Sylvia Lucas ◽  
Nadège Télef-Micouleau ◽  
Jean-Michel Mérillon ◽  
...  
Keyword(s):  
Defense Response ◽  
Defense Mechanisms ◽  
Defense Responses ◽  
Cabernet Sauvignon ◽  
Susceptible Cultivar ◽  
Pathogenesis Related ◽  
Leaf Level ◽  
Plant Pathogen Interaction ◽  
Related Proteins ◽  
Stilbene Compounds

Wood diseases like Esca are among the most damaging afflictions in grapevine. The defense mechanisms in this plant–pathogen interaction are not well understood. As some grapevine cultivars have been observed to be less susceptible to Esca than others, understanding the factors involved in this potentially stronger defense response can be of great interest. To lift part of this veil, we elicited Vitis vinifera plants of two cultivars less susceptible to Esca (‘Merlot’ and ‘Carignan’) and of one susceptible cultivar (‘Cabernet Sauvignon’), and monitored their defense responses at the leaf level. Our model of elicitation consisted in grapevine cuttings absorbing a culture filtrate of one causal agent of Esca, Phaemoniella chlamydospora. This model might reflect the early events occurring in Esca-affected grapevines. The two least susceptible cultivars showed an earlier and stronger defense response than the susceptible one, particularly with regard to induction of the PAL and STS genes, and a higher accumulation of stilbene compounds and some pathogenesis-related proteins.

scholarly journals Diversity of molecular mechanisms used by anti-CRISPR proteins: the tip of an iceberg?

2020 ◽  
Vol 48 (2) ◽  
pp. 507-516 ◽  
Author(s):  
Pierre Hardouin ◽  
Adeline Goulet
Keyword(s):  
Immune System ◽  
Structure Function ◽  
Defense Mechanisms ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Arms Race ◽  
Allosteric Inhibitors ◽  
Fundamental Knowledge ◽  
Attack And Defense ◽  
Fine Tune

Bacteriophages (phages) and their preys are engaged in an evolutionary arms race driving the co-adaptation of their attack and defense mechanisms. In this context, phages have evolved diverse anti-CRISPR proteins to evade the bacterial CRISPR–Cas immune system, and propagate. Anti-CRISPR proteins do not share much resemblance with each other and with proteins of known function, which raises intriguing questions particularly relating to their modes of action. In recent years, there have been many structure–function studies shedding light on different CRISPR–Cas inhibition strategies. As the anti-CRISPR field of research is rapidly growing, it is opportune to review the current knowledge on these proteins, with particular emphasis on the molecular strategies deployed to inactivate distinct steps of CRISPR–Cas immunity. Anti-CRISPR proteins can be orthosteric or allosteric inhibitors of CRISPR–Cas machineries, as well as enzymes that irreversibly modify CRISPR–Cas components. This repertoire of CRISPR–Cas inhibition mechanisms will likely expand in the future, providing fundamental knowledge on phage–bacteria interactions and offering great perspectives for the development of biotechnological tools to fine-tune CRISPR–Cas-based gene edition.

scholarly journals Receptors That Inhibit Macrophage Activation: Mechanisms and Signals of Regulation and Tolerance

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Ranferi Ocaña-Guzman ◽  
Luis Vázquez-Bolaños ◽  
Isabel Sada-Ovalle
Keyword(s):  
Immune System ◽  
Cell Lines ◽  
Immune Tolerance ◽  
Defense Mechanisms ◽  
Macrophage Activation ◽  
Immunological Tolerance ◽  
Innate Defense ◽  
Activation Mechanisms ◽  
Monocytes And Macrophages ◽  
Inhibitory Molecules

A variety of receptors perform the function of attenuating or inhibiting activation of cells in which they are expressed. Examples of these kinds of receptors include TIM-3 and PD-1, among others that have been widely studied in cells of lymphoid origin and, though to a lesser degree, in other cell lines. Today, several studies describe the function of these molecules as part of the diverse mechanisms of immune tolerance that exist in the immune system. This review analyzes the function of some of these proteins in monocytes and macrophages and as well as their participation as inhibitory molecules or elements of immunological tolerance that also act in innate defense mechanisms. We chose the receptors TIM-3, PD-1, CD32b, and CD200R because these molecules have distinct functional characteristics that provide examples of the different regulating mechanisms in monocytes and macrophages.

scholarly journals Small molecules, big effects: microbial metabolites in intestinal immunity

2020 ◽  
Vol 318 (5) ◽  
pp. G907-G911
Author(s):  
Lila G. Glotfelty ◽  
Andrea C. Wong ◽  
Maayan Levy
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Microbial Community ◽  
Small Molecules ◽  
Defense Mechanisms ◽  
Microbial Metabolites ◽  
Intestinal Immunity ◽  
Vast Number ◽  
Health And Disease ◽  
Mammalian Intestine

The mammalian intestine is host to a vast number of microbial organisms. The immune system must balance tolerance with innate and adaptive defense mechanisms to maintain homeostasis with the microbial community. Interestingly, microbial metabolites have been shown to play a role in shaping the host immune response, thus assisting with adaptations that have significant implications for human health and disease. New investigations have uncovered roles for metabolites in modulating almost every aspect of the immune system. In this minireview, we survey these recent findings, which taken together reveal nuanced interactions that we are just beginning to understand.

Influence of metabolic status and genetic merit for fertility on proteomic composition of bovine oviduct fluid†

2019 ◽  
Vol 101 (5) ◽  
pp. 893-905 ◽  
Author(s):  
Katrin Gegenfurtner ◽  
Thomas Fröhlich ◽  
Miwako Kösters ◽  
Pascal Mermillod ◽  
Yann Locatelli ◽  
...  
Keyword(s):  
Immune System ◽  
Genetic Predisposition ◽  
Genetic Model ◽  
Metabolic Stress ◽  
Metabolic Model ◽  
Early Embryo ◽  
Mass Spectrometry Analysis ◽  
Embryonic Loss ◽  
Oviduct Fluid ◽  
Related Proteins

Abstract The oviduct plays a crucial role in fertilization and early embryo development providing the microenvironment for oocyte, spermatozoa, and early embryo. Since dairy cow fertility declined steadily over the last decades, reasons for early embryonic loss have gained increasing interest. Analyzing two animal models, this study aimed to investigate the impact of genetic predisposition for fertility and of metabolic stress on the protein composition of oviduct fluid. A metabolic model comprised maiden Holstein heifers and postpartum lactating (Lact) and non-lactating (Dry) cows, while a genetic model consisted of heifers from the Montbéliarde breed and Holstein heifers with low- and high-fertility index. In a holistic proteomic analysis of oviduct fluid from all groups using nano-liquid chromatography tandem-mass spectrometry analysis and label-free quantification, we were able to identify 1976 proteins, among which 143 showed abundance alterations in the pairwise comparisons within both models. Most differentially abundant proteins were revealed between low fertility Holstein and Montbéliarde (52) in the genetic model and between lactating and maiden Holstein (19) in the metabolic model, demonstrating a substantial effect of genetic predisposition for fertility and metabolic stress on the oviduct fluid proteome. Functional classification of affected proteins revealed actin binding, translation, and immune system processes as prominent gene ontology (GO) clusters. Notably, Actin-related protein 2/3 complex subunit 1B and the three immune system-related proteins SERPIND1 protein, immunoglobulin kappa locus protein, and Alpha-1-acid glycoprotein were affected in both models, suggesting that abundance changes of immune-related proteins in oviduct fluid play an important role for early embryonic loss.

scholarly journals The MHC Class Ia Genes in Chenfu’s Treefrog (Zhangixalus chenfui) Evolved via Gene Duplication, Recombination, and Selection

Animals ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 34
Author(s):  
Hu Chen ◽  
Siqi Huang ◽  
Ye Jiang ◽  
Fuyao Han ◽  
Qingyong Ni ◽  
...  
Keyword(s):  
Gene Duplication ◽  
Positive Selection ◽  
Phylogenetic Relationships ◽  
Molecular Mechanisms ◽  
Coding Region ◽  
Evolutionary Mechanisms ◽  
Evolutionary Patterns ◽  
Mhc Genes ◽  
Mhc Class Ia ◽  
Related Proteins

The molecular mechanisms underlying the evolution of adaptive immunity-related proteins can be deduced by a thorough examination of the major histocompatibility complex (MHC). Currently, in vertebrates, there is a relatively large amount of research on MHCs in mammals and birds. However, research related to amphibian MHC genes and knowledge about the evolutionary patterns is limited. This study aimed to isolate the MHC class I genes from Chenfu’s Treefrog (Zhangixalus chenfui) and reveal the underlying evolutionary processes. A total of 23 alleles spanning the coding region of MHC class Ia genes were identified in 13 individual samples. Multiple approaches were used to test and identify recombination from the 23 alleles. Amphibian MHC class Ia alleles, from NCBI, were used to construct the phylogenetic relationships in MEGA. Additionally, the partition strategy was adopted to construct phylogenetic relationships using MrBayes and MEGA. The sites of positive selection were identified by FEL, PAML, and MEME. In Chenfu’s Treefrog, we found that: (1) recombination usually takes place between whole exons of MHC class Ia genes; (2) there are at least 3 loci for MHC class Ia, and (3) the diversity of genes in MHC class Ia can be attributed to recombination, gene duplication, and positive selection. We characterized the evolutionary mechanisms underlying MHC class Ia genes in Chenfu’s Treefrog, and in so doing, broadened the knowledge of amphibian MHC systems.

scholarly journals Cadmium-Related Effects on Cellular Immunity Comprises Altered Metabolism in Earthworm Coelomocytes

2020 ◽  
Vol 21 (2) ◽  
pp. 599 ◽  
Author(s):  
Martina Höckner ◽  
Claudio Adriano Piechnik ◽  
Birgit Fiechtner ◽  
Birgit Weinberger ◽  
Lars Tomanek
Keyword(s):  
Immune System ◽  
Energy Demand ◽  
Cell Protein ◽  
Metabolic Potential ◽  
Extracellular Flux ◽  
Potential Link ◽  
Flux Measurements ◽  
Acute Changes ◽  
Related Proteins ◽  
Cd Exposure

The heavy metal cadmium (Cd) is known to modulate the immune system, challenging soil-dwelling organisms where environmental Cd pollution is high. Since earthworms lack adaptive immunity, we determined Cd-related effects on coelomocytes, the cellular part of innate immunity, which is also the site of detoxification processes. A proteomics approach revealed a set of immunity-related proteins as well as gene products involved in energy metabolism changing in earthworms in response to Cd exposure. Based on these results, we conducted extracellular flux measurements of oxygen and acidification to reveal the effect of Cd on coelomocyte metabolism. We observed a significantly changing oxygen consumption rate, extracellular acidification, as well as metabolic potential, which can be defined as the response to an induced energy demand. Acute changes in intracellular calcium levels were also observed, indicating impaired coelomocyte activation. Lysosomes, the cell protein recycling center, and mitochondrial parameters did not change. Taken together, we were able to characterize coelomocyte metabolism to reveal a potential link to an impaired immune system upon Cd exposure.

scholarly journals Flea-Borne Transmission Model To Evaluate Vaccine Efficacy against Naturally Acquired Bubonic Plague

2004 ◽  
Vol 72 (4) ◽  
pp. 2052-2056 ◽  
Author(s):  
Clayton O. Jarrett ◽  
Florent Sebbane ◽  
Jeffrey J. Adamovicz ◽  
Gerard P. Andrews ◽  
B. Joseph Hinnebusch
Keyword(s):  
Immune System ◽  
Fusion Protein ◽  
Vaccine Efficacy ◽  
Systemic Infection ◽  
Transmission Model ◽  
Serological Testing ◽  
Protein Vaccine ◽  
Bubonic Plague ◽  
Unvaccinated Control ◽  
New Vaccines

ABSTRACT A flea-to-mouse transmission model was developed for use in testing new candidate vaccines for the ability to protect against flea-borne plague. The model was used to evaluate a recombinant fusion protein vaccine consisting of the Yersinia pestis F1 and V antigens. After one to three challenges with Y. pestis-infected fleas, 14 of 15 unvaccinated control mice developed plague, with an average septicemia level of 9.2 × 108 Y. pestis CFU/ml. None of 15 vaccinated mice developed the disease after similar challenges, and serological testing indicated that transmitted bacteria were eliminated by the immune system before extensive replication and systemic infection could occur. The transmission and development of disease in control mice correlated with the number of bites by blocked fleas but not with the total number of fleabites. The model provides a means to directly assess the efficacy of new vaccines to prevent naturally acquired bubonic plague and to study events at the vector-host interface that lead to dissemination and disease.

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