| 1. |
- Akula, Srinivas, et al.
(författare)
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Analysis of the mast cell expressed carboxypeptidase A3 and its structural and evolutionary relationship to other vertebrate carboxypeptidases
- 2022
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Ingår i: Developmental and Comparative Immunology. - : Elsevier. - 0145-305X .- 1879-0089. ; 127
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Tidskriftsartikel (refereegranskat)abstract
- Metallo-carboxypeptidases are exopeptidases with diverse expression and function, found in all kingdoms of life from bacteria to mammals. One of them, the carboxypeptidase A3 (CPA3), has become an important component of the mammalian immune system by its expression in mast cells. Mast cells (MCs) are highly specialized sentinel cells, which store large amounts of bioactive mediators, including CPA3, in very abundant cytoplasmic granules. Clinical studies have found an increased CPA3 expression in asthma but the physiological role as well as the evolutionary origin of CPA3 remains largely unexplored. CPA3 belongs to the M14A subfamily of metallocarboxypeptidases, which among others also includes the digestive enzymes CPA1, CPA2, CPB1 and CPO. To study the appearance of CPA3 during vertebrate evolution, we here performed bioinformatic analyses of homologous genes and gene loci from a broad panel of metazoan animals from invertebrates to mammals. The phylogenetic analysis indicated that CPA3 appeared at the base of tetrapod evolution in a branch closer to CPB1 than to other CPAs. Indeed, CPA3 and CPB1 are also located in the same locus, on chromosome 3 in humans. The presence of CPA3 only in tetrapods and not in fishes, suggested that CPA3 could have appeared by a gene duplication from CPB1 during early tetrapod evolution. However, the apparent loss of CPA3 in several tetrapod lineages, e.g. in birds and monotremes, indicates a complex evolution of the CPA3 gene. Interestingly, in the lack of CPA3 in fishes, zebrafish MCs express instead CPA5 for which the most closely related human carboxypeptidase is CPA1, which has a similar cleavage specificity as CPA3. Collectively, these findings clarify and add to our understanding of the evolution of hematopoietic proteases expressed by mast cells.
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| 2. |
- Aybay, Erdem, et al.
(författare)
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Two granzyme A/K homologs in Zebra mbuna have different specificities, one classical tryptase and one with chymase activity
- 2023
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Ingår i: Developmental and Comparative Immunology. - : Elsevier. - 0145-305X .- 1879-0089. ; 148
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Tidskriftsartikel (refereegranskat)abstract
- Granzymes A and K are two highly homologous serine proteases expressed by mammalian cytotoxic T cells (CTLs) and natural killer (NK) cells. The locus encoding these two proteases is the first of the hematopoietic serine protease loci to appear during vertebrate evolution. This locus is found in all jawed vertebrates including the cartilaginous fishes. Granzyme A is the most abundant of the different granzymes expressed by CTLs and NK cells and its potential function has been studied extensively for many years. However, no clear conclusions concerning its primary role in the immune defense has been obtained. In all mammals, there are only one copy each of granzyme A and K, whereas additional copies are found in both cartilaginous and ray finned fishes. In cichlids two of these copies seem to encode new members of the granzyme A/K family. These two new members appear to have changed primary specificity and to be pure chymases based on the amino acids in their active site substrate binding pockets. Interestingly, one of these gene copies is located in the middle of the granzyme A/K locus, while the other copy is present in another locus, the met-ase locus. We here present a detailed characterization of the extended cleavage specificity of one of these non-classical granzymes, a Zebra mbuna granzyme positioned in the granzyme A/K locus. This enzyme, named granzyme A2, showed a high preference for tyrosine in the P1 position of substrates, thereby being a strict chymase. We have also characterized one of the classical granzyme A/Ks of the Zebra mbuna, granzyme A1, which is a tryptase with preference for arginine in the P1 position of substrates. Based on their extended specificities, the two granzymes showed major similarities, but also some differences in preferred amino acids in positions surrounding the cleavable amino acid. Fish lack one of the hematopoietic serine protease loci of mammals, the chymase locus, where one of the major mast cell enzymes is located. An interesting question is now if cichlids have by compensatory mechanisms generated a mast cell chymase from another locus, and if similar chymotryptic enzymes have appeared also in other fish species.
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| 3. |
- Baruah, Kartik
(författare)
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Phloroglucinol shows prophylactic and metaphylactic effects against pathogenic stressors in Macrobrachium larvae
- 2022
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Ingår i: Developmental and Comparative Immunology. - : Elsevier BV. - 0145-305X .- 1879-0089. ; 128
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Tidskriftsartikel (refereegranskat)abstract
- Vibriosis caused by Vibrio campbellii and related species is amongst the major hindrance to the sustainable expansion of giant freshwater prawn Macrobrachium rosenbergii larviculture. Induction of heat shock protein Hsp70 is a natural response of stressed organisms that protect against many insults including vibriosis in aquaculture animals. Therefore, there is a great interest in searching for natural compounds that could induce Hsp70 in animals in a non-invasive manner. Previously, in a series of in vivo studies, we have shown that the phenolic compound phloroglucinol could induce Hsp70 in aquaculture organisms Macrobrachium and Artemia. This led to a significant increase in the resistance of the animals towards subsequent challenges with V. parahemolyticus. As V. parahaemolyticus belongs to the Harveyi clade similar to V. campbellii, our above findings triggered the hypothesis that phloroglucinol is a potential anti-microbial agent that could protect the freshwater prawn against V. campbellii infection. The results presented here provide evidence that the Hsp70-inducing compound phloroglucinol could induce both metaphylactic and prophylactic effects against infection stress mediated by V. campbellii. The wide-spectrum property of the compound to both prevent the occurrence and reduce the spread of V. campbellii infection in prawn larvae without affecting the larval growth makes it a potential natural agent for health management and V. campbellii-mediated disease control in freshwater prawn larvae. Overall results add new information about the functional properties of phloroglucinol and advance our knowledge of this compound as a potential antimicrobial agent for the sustainable production of giant freshwater prawns.
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| 4. |
- Cerenius, Lage, 1956-, et al.
(författare)
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Immune properties of invertebrate phenoloxidases
- 2021
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Ingår i: Developmental and Comparative Immunology. - : Elsevier. - 0145-305X .- 1879-0089. ; 122
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Forskningsöversikt (refereegranskat)abstract
- Melanin production from different types of phenoloxidases (POs) confers immunity from a variety of pathogens ranging from viruses and microorganisms to parasites. The arthropod proPO expresses a variety of activities including cytokine, opsonin and microbiocidal activities independent of and even without melanin production. Proteolytic processing of proPO and its activating enzyme gives rise to several peptide fragments with a variety of separate activities in a process reminiscent of vertebrate complement system activation although proPO bears no sequence similarity to vertebrate complement factors. Pathogens influence proPO activation and thereby what types of immune effects that will be produced. An increasing number of specialised pathogens - from parasites to viruses - have been identified who can synthesise compounds specifically aimed at the proPO-system. In invertebrates outside the arthropods phylogenetically unrelated POs are participating in melanization reactions obviously aimed at intruders and/or aberrant tissues.
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| 5. |
- Fu, Zhirong, et al.
(författare)
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Chicken cathepsin G-like - A highly specific serine protease with a peculiar tryptase specificity expressed by chicken thrombocytes
- 2022
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Ingår i: Developmental and Comparative Immunology. - : Elsevier. - 0145-305X .- 1879-0089. ; 129
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Tidskriftsartikel (refereegranskat)abstract
- Serine proteases are major granule constituents of cells from several mammalian hematopoietic cell lineages. Despite the relatively extensive knowledge about these mammalian proteases, very little is known about their bird, reptile and amphibian homologs. In order to close this gap in our understanding of the evolution of these proteases, we have characterized the extended cleavage specificity and hematopoietic expression pattern of the chicken serine protease cathepsin G-like. This protease, which clusters in a separate subfamily of serine proteases among the vertebrate hematopoietic serine proteases, has been characterized using substrate phage display and further validated by using a panel of recombinant substrates. A preference for a lysine in the P1 position of a substrate, arginines in positions P2 and P3, and the aromatic amino acid tryptophane in the P4 position was observed. Based on the sequence alignment we could identify a consensus sequence for this protease as being PGGWRRK(down arrow & nbsp;)ALSV. Mass spectrometry analysis of a peptide with the consensus sequence obtained by phage display showed that cleavage of this peptide occurred after the conserved Lys (K) residue. A screening of potential in vivo substrates based on the derived P5-P3' consensus sequence resulted in a relatively limited number of potential substrates, due to the high selectivity of this enzyme. The most interesting of these were PDGF-A, coagulation factor V and low-density lipoprotein receptor like-8. Immunohistochemical analysis of chicken white blood cells with antisera produced against chicken cathepsin G-like and chicken egg lysozyme, as a reference protein known to be expressed by hematopoietic cells, showed presence of chicken cathepsin G-like almost exclusively in thrombocytes whereas lysozyme was found at very high amounts in heterophils, and lower amounts in monocytes and thrombocytes.
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| 6. |
- Gabor, Erika, et al.
(författare)
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Identification of reference markers for characterizing honey bee (Apis mellifera) hemocyte classes
- 2020
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Ingår i: Developmental and Comparative Immunology. - : Elsevier BV. - 0145-305X .- 1879-0089. ; 109
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Tidskriftsartikel (refereegranskat)abstract
- Cell mediated immunity of the honey bee (Apis mellifera) involves the activity of several hemocyte populations, currently defined by morphological features and lectin binding characteristics. The objective of the present study was to identify molecular markers capable of characterizing subsets of honey bee hemocytes. We developed and employed monoclonal antibodies with restricted reactions to functionally distinct hemocyte subpopulations. Melanizing cells, known as oenocytoids, were defined by an antibody to prophenoloxidase, aggregating cells were identified by the expression of Hemolectin, and phagocytic cells were identified by a marker expressed on granulocytes. We anticipate that this combination of antibodies not only allows for the detection of functionally distinct hemocyte subtypes, but will help to further the exploration of hematopoietic compartments, as well as reveal details of the honey bee cellular immune defense against parasites and microbes.
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| 7. |
- Guabiraba, Rodrigo, et al.
(författare)
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Mechanisms of type I interferon production by chicken TLR21
- 2024
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Ingår i: Developmental and comparative immunology. - 1879-0089. ; 151
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Tidskriftsartikel (refereegranskat)abstract
- The innate immune response relies on the ability of host cells to rapidly detect and respond to microbial nucleic acids. Toll-like receptors (TLRs), a class of pattern recognition receptors (PRRs), play a fundamental role in distinguishing self from non-self at the molecular level. In this study, we focused on TLR21, an avian TLR that recognizes DNA motifs commonly found in bacterial genomic DNA, specifically unmethylated CpG motifs. TLR21 is believed to act as a functional homologue to mammalian TLR9. By analysing TLR21 signalling in chickens, we sought to elucidate avian TLR21 activation outputs in parallel to that of other nucleic acid species. Our analyses revealed that chicken TLR21 (chTLR21) triggers the activation of NF-κB and induces a potent type-I interferon response in chicken macrophages, similar to the signalling cascades observed in mammalian TLR9 activation. Notably, the transcription of interferon beta (IFNB) by chTLR21 was found to be dependent on both NF-κB and IRF7 signalling, but independent of the TBK1 kinase, a distinctive feature of mammalian TLR9 signalling. These findings highlight the conservation of critical signalling components and downstream responses between avian TLR21 and mammalian TLR9, despite their divergent evolutionary origins. These insights into the evolutionarily conserved mechanisms of nucleic acid sensing contribute to the broader understanding of host-pathogen interactions across species.
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| 8. |
- Hernandez-Perez, Ariadne, et al.
(författare)
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Gut microbiome alterations in the crustacean Pacifastacus leniusculus exposed to environmental concentrations of antibiotics and effects on susceptibility to bacteria challenges*
- 2022
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Ingår i: Developmental and Comparative Immunology. - : Elsevier. - 0145-305X .- 1879-0089. ; 126
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Tidskriftsartikel (refereegranskat)abstract
- Gut-associated microbiota in crustaceans are recognized as a key element for maintaining homeostasis and health in the animal. Since the richness of these microbial communities is strongly influenced by the local environment, especially in aquatic organisms, it is important to address to what extent environmental variations can affect these communities. In the present study, we used high-throughput 16S rRNA sequencing technology to study the composition of gut-associated microbiota of the crayfish Pacifastacus leniusculus after exposure to environmentally-relevant concentrations of an antibiotic, namely sulfamethoxazole. Also, we examined if alterations of microbiota caused by environmentally-relevant concentrations of this antibiotic affected the host susceptibility to bacterial diseases, including Vibrio species. As a result, we found high individual variability of bacterial abundance and composition in the intestinal microbiome of crayfish, in both antibiotic-exposed and antibiotic-free crayfish. However, an increase of chitinolytic bacteria including Vibrio spp. was detected in some animals exposed to the antibiotic. Moreover, when crayfish susceptibility to bacterial infections was tested, the antibiotic-exposed crayfish survived longer than the control crayfish group. This study represents the first approach for investigating the interplay between crayfish and intestinal bacteria during antibiotic-pollution scenarios. Results herein should be considered by scientists before planning experiments under laboratory conditions, especially to study environmental effects on aquatic animals' intestinal health and immune status.
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| 9. |
- Hernandez-Perez, Ariadne, et al.
(författare)
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Intestinal microbiome in crayfish : Its role upon growth and disease presentation
- 2023
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Ingår i: Developmental and Comparative Immunology. - : ELSEVIER SCI LTD. - 0145-305X .- 1879-0089. ; 145
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Tidskriftsartikel (refereegranskat)abstract
- The intestine-associated microbiota in crustaceans are considered a key element for maintaining homeostasis and health within the organisms. Recently, efforts have been made to characterize bacterial communities of freshwater crustaceans, including crayfish, and their interplay with the host's physiology and the aquatic environments. As a result, it has become evident that crayfish intestinal microbial communities display high plasticity, which is strongly influenced by both the diet, especially in aquaculture, and the environment. Moreover, studies regarding the characterization and distribution of the microbiota along the gut portions led to the discovery of bacteria with probiotic potential. The addition of these microorganisms to their food has shown a limited positive correlation with the growth and development of crayfish freshwater species. Finally, there is evidence that infections, particularly those from viral etiology, lead to low diversity and abundance of the intestinal microbial communities. In the present article, we have reviewed data on the crayfish' intestinal microbiota, highlighting the most frequently observed taxa and emphasizing the dominance of phylum within this community. In addition, we have also searched for evidence of microbiome manipulation and its potential impact on productive parameters, and discussed the role of the microbiome in the regulation of diseases presentation, and environmental perturbations.
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| 10. |
- Hernroth, Bodil, et al.
(författare)
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Immunosuppression of aquatic organisms exposed to elevated levels of manganese: From global to molecular perspective
- 2020
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Ingår i: Developmental and Comparative Immunology. - : Elsevier BV. - 0145-305X .- 1879-0089. ; 104
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Tidskriftsartikel (refereegranskat)abstract
- Manganese (Mn) is an essential trace metal for all organisms. However, in excess it causes toxic effects but the impact on aquatic environments has so far been highly overlooked. Manganese is abundant both in costal and deep sea sediments and becomes bioavailable (Mn2+) during redox conditions. This is an increasing phenomenon due to eutrophication-induced hypoxia and aggravated through the ongoing climate change. Intracellular accumulation of Mn2+ causes oxidative stress and activates evolutionary conserved pathways inducing apoptosis and cell cycle arrest. Here, studies are compiled on how excess of dissolved Mn suppresses the immune system of various aquatic organisms by adversely affecting both renewal of immunocytes and their functionality, such as phagocytosis and activation of pro-phenoloxidase. These impairments decrease the animal's bacteriostatic capacity, indicating higher susceptibility to infections. Increased distribution of pathogens, which is believed to accompany climate change, requires preserved immune sentinel functions and Mn can be crucial for the outcome of host-pathogen interactions.
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