Hepatitis B virus (HBV) infection can cause liver disease and lead to hepatocellular carcinoma (HCC). To better understand the factors involved in viral infection and pathogenesis and to develop novel therapies, it is crucial to investigate virus-host interactions. HBV infection has been shown to increase the expression of the unconventional prefoldin RPB5 interactor (URI1), a cellular protein that promotes liver tumorigenesis and HCC metastasis. Our study investigated the role of URI1 in HBV infection in vitro. Although previous reports have suggested that URI1 may act as an HBV restriction factor, our results showed that URI1 silencing or overexpression did not affect HBV replication in HepG2-NTCP cells. In primary human hepatocytes, URI1 knockdown modestly reduced HBV markers but did not significantly alter acute infection. Supporting the premise that URI1 is a promising therapeutic target for HCC, our findings show that URI1 knockdown does not enhance HBV infection in an acute infection model. This suggests that URI1 may be a viable therapeutic target for patients with HBV-associated HCC without increasing HBV-related complications.
- MeSH
- Hep G2 Cells MeSH
- Gene Knockdown Techniques MeSH
- Hepatitis B * virology complications metabolism MeSH
- Carcinoma, Hepatocellular virology metabolism MeSH
- Hepatocytes * virology metabolism MeSH
- Host-Pathogen Interactions MeSH
- Humans MeSH
- Virus Replication * MeSH
- Hepatitis B virus * genetics physiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Mikroorganismy si během evoluce vyvinuly širokou škálu strategií, jak uniknout vrozenému i adaptivnímu imunitnímu systému, a některým těmto strategiím se věnujeme v našem přehledu. Mikroorganismy mohou využívat podobnost svých proteinů s proteiny hostitele, produkovat protizánětlivé faktory, narušovat komplementový systém, ovlivňovat funkci a blokovat syntézu cytokinů, inhibovat rozpoznávání imunoglobulinů, snižovat expresi a modifikovat antigeny na svém povrchu, narušovat zpracování a prezentaci antigenu imunitními buňkami, vstupovat do imunitních buněk, ovlivňovat apoptózu buněk, modulovat funkce imunitních buněk nebo ovlivňovat produkci hormonů. S těmito únikovými strategiemi je nutné počítat při léčbě infekčních onemocnění.
Microorganisms have evolved a wide variety of strategies to evade both the innate and adaptive immune systems during evolution, and some of these strategies are addressed in our review. Microorganisms can use the similarity of their proteins to host proteins, produce anti-inflammatory factors, disrupt the complement system, affect the function and block the synthesis of cytokines, inhibit the recognition of immunoglobulins, reduce the expression and modify antigens on their surface, disrupt the processing and presentation of antigen by immune cells, enter immune cells , influence cell apoptosis, modulate immune cell functions or influence hormone production. These escape strategies must be taken into account when treating infectious diseases.
- Keywords
- únikové strategie mikroorganismů,
- MeSH
- Host-Pathogen Interactions MeSH
- Humans MeSH
- Microbiological Phenomena * MeSH
- Immunity, Innate * MeSH
- Trained Immunity MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
The two stork species that nest in Central Europe, Ciconia ciconia and Ciconia nigra, have been repeatedly shown to host the digenetic trematode Cathaemasia hians (Rudolphi, 1809) in their esophagus and muscular stomach. These host species differ in their habitat and food preferences, and the morphologic characters of C. hians isolates ex Ci. nigra and Ci. ciconia are not identical. These differences led to a previous proposal of two subspecies, Cathaemasia hians longivitellata Macko, 1960, and Cathaemasia hians hians Macko, 1960. We hypothesize that the Cathaemasia hians isolates ex Ci. nigra and Ci. ciconia represent two independent species. Therefore, in the present study, we performed the first molecular analyses of C. hians individuals that were consistent with the diagnosis of C. hians hians (ex Ci. nigra) and C. hians longivitellata (ex Ci. ciconia). The combined molecular and comparative morphological analyses of the central European Cathaemasia individuals ex Ci. nigra and Ci. ciconia led to the proposal of a split of C. hians into C. hians sensu stricto (formerly C. hians hians) and C. longivitellata sp. n. (formerly C. hians longivitellata). Morphological analyses confirmed that the length of the vitellaria is the key identification feature of the two previously mentioned species. Both Cathaemasia spp. substantially differ at the molecular level and have strict host specificity, which might be related to differences in the habitat and food preferences of the two stork species.
- MeSH
- DNA, Helminth genetics MeSH
- Species Specificity MeSH
- Phylogeny * MeSH
- Host Specificity * MeSH
- Birds parasitology MeSH
- Trematoda * anatomy & histology classification genetics MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
Bordetella pertussis is the causative agent of whooping cough in humans, a disease that has recently experienced a resurgence. In contrast, Bordetella bronchiseptica infects the respiratory tract of various mammalian species, causing a range of symptoms from asymptomatic chronic carriage to acute illness. Both pathogens utilize type III secretion system (T3SS) to deliver the effector protein BteA into host cells. Once injected, BteA triggers a cascade of events leading to caspase 1-independent necrosis through a mechanism that remains incompletely understood. We demonstrate that BteA-induced cell death is characterized by the fragmentation of the cellular endoplasmic reticulum and mitochondria, the formation of necrotic balloon-like protrusions, and plasma membrane permeabilization. Importantly, genome-wide CRISPR-Cas9 screen targeting 19,050 genes failed to identify any host factors required for BteA cytotoxicity, suggesting that BteA does not require a single nonessential host factor for its cytotoxicity. We further reveal that BteA triggers a rapid and sustained influx of calcium ions, which is associated with organelle fragmentation and plasma membrane permeabilization. The sustained elevation of cytosolic Ca2+ levels results in mitochondrial calcium overload, mitochondrial swelling, cristolysis, and loss of mitochondrial membrane potential. Inhibition of calcium channels with 2-APB delays both the Ca2+ influx and BteA-induced cell death. Our findings indicate that BteA exploits essential host processes and/or redundant pathways to disrupt calcium homeostasis and mitochondrial function, ultimately leading to host cell death.IMPORTANCEThe respiratory pathogens Bordetella pertussis and Bordetella bronchiseptica exhibit cytotoxicity toward a variety of mammalian cells, which depends on the type III secretion effector BteA. Moreover, the increased virulence of B. bronchiseptica is associated with enhanced expression of T3SS and BteA. However, the molecular mechanism underlying BteA cytotoxicity is elusive. In this study, we performed a CRISPR-Cas9 screen, revealing that BteA-induced cell death depends on essential or redundant host processes. Additionally, we demonstrate that BteA disrupts calcium homeostasis, which leads to mitochondrial dysfunction and cell death. These findings contribute to closing the gap in our understanding of the signaling cascades targeted by BteA.
- MeSH
- Bacterial Proteins * metabolism genetics MeSH
- Bordetella bronchiseptica genetics metabolism drug effects MeSH
- Bordetella pertussis genetics pathogenicity metabolism drug effects MeSH
- Cell Death * drug effects MeSH
- Endoplasmic Reticulum metabolism drug effects MeSH
- Homeostasis * MeSH
- Host-Pathogen Interactions MeSH
- Humans MeSH
- Mitochondria metabolism drug effects MeSH
- Type III Secretion Systems metabolism genetics MeSH
- Calcium * metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Schistosoma mansoni was introduced from Africa to the Americas during the transatlantic slave trade and remains a major public health problem in parts of South America and the Caribbean. This study presents a comprehensive comparative analysis of three S. mansoni strains with different geographical origins-from Liberia, Belo Horizonte and Puerto Rico. We demonstrated significant variation in virulence and host-parasite interactions. METHODS: We investigated the phenotypic characteristics of the parasite and its eggs, as well as the immunopathologic effects on laboratory mouse organ systems. RESULTS: Our results show significant differences in worm morphology, worm burden, egg size, and pathologic organ changes between these strains. The Puerto Rican strain showed the highest virulence, as evidenced by marked liver and spleen changes and advanced liver fibrosis indicated by increased collagen content. In contrast, the strains from Liberia and Belo Horizonte had a less pathogenic profile with less liver fibrosis. We found further variations in granuloma formation, cytokine expression and T-cell dynamics, indicating different immune responses. CONCLUSION: Our study emphasizes the importance of considering intra-specific variations of S. mansoni for the development of targeted therapies and public health strategies. The different virulence patterns, host immune responses and organ pathologies observed in these strains provide important insights for future research and could inform region-specific interventions for schistosomiasis control.
- MeSH
- Cytokines metabolism MeSH
- Host-Parasite Interactions MeSH
- Liver * parasitology pathology MeSH
- Mice MeSH
- Schistosoma mansoni * pathogenicity genetics immunology MeSH
- Schistosomiasis mansoni * parasitology immunology pathology MeSH
- Spleen parasitology pathology immunology MeSH
- Virulence MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Liberia MeSH
- Puerto Rico MeSH
Trematodes of the order Diplostomida are well known as serious pathogens of man, and both farm and wild animals; members of the genus Schistosoma (Schistosomatidae) are responsible for human schistosomosis (schistosomiasis) affecting more than 200 million people in tropical and subtropical countries, and infections of mammals and birds by animal schistosomes are of great veterinary importance. The order Diplostomida is also rich in species parasitizing other major taxa of vertebrates. The "Aporocotylidae" sensu lato are pathogenic in fish, "Spirorchiidae" sensu lato in reptiles. All these flukes have two-host life cycles, with asexually reproducing larvae usually in mollusks and occasionally in annelids, and adults usually live in the blood vessels of their vertebrate hosts. Pathology is frequently associated with inflammatory reactions to eggs trapped in various tissues/organs. On the other hand, the representatives of Diplostomidae and Strigeidae have three- or four-host life cycles in which vertebrates often serve not only as definitive but also as intermediate or paratenic hosts. Pathology is usually associated with migration of metacercariae and mesocercariae within the host tissues. The impact of these trematode infections on both farm and wild animals may be significant.
Multivalvulidan myxosporeans (Multivalvulida) of the genera Unicapsula Davis, 1924 and Kudoa Meglitsch, 1947 are mostly causative agents of latent and imperceptible infection in marine fishes. However, they are sometimes incriminated in causing post-mortem myoliquefaction or unsightly cyst formation in commercial fish. Despite the great commercial impacts of multivalvulidan infection, the biodiversity, host range and epidemiology of multivalvulidan species remain to be explored further, including infection of alternative annelid hosts. Therefore, this study aimed to identify multivalvulidan species and their host and/or distribution records in commercial fishes in China. Multivalvulidan infection was detected in ten commercial fish species of seven families from the South and East China Seas (Northwest Pacific Ocean) and the Eastern Central Atlantic Ocean (an imported Dagetichthys lusitanicus [de Brito Capello]). Based on morphological and molecular-genetic analyses of their small and large subunit of ribosomal RNA genes, five new host and/or geographical distribution records for five fish species are presented, and three new species in five fish species are described, namely Kudoa neoscomberomori sp. n. in Scomberomorus commerson (Lacépède); Kudoa pilosa sp. n. in Helicolenus hilgendorfi (Döderlein) (type host) and Sebastiscus tertius (Barsukov et Chen); and Kudoa tumidisporica sp. n. in Photopectoralis bindus (Valenciennes) (type host) and Nuchequula nuchalis (Temminck et Schlegel). This study provides new data on multivalvulidan diversity in the ocean ecosystem.
- MeSH
- Phylogeny * MeSH
- Host Specificity MeSH
- Myxozoa * classification genetics isolation & purification MeSH
- Fish Diseases * parasitology epidemiology MeSH
- Parasitic Diseases, Animal * parasitology epidemiology MeSH
- Fishes * parasitology MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- China MeSH
In this review, I take the first-person perspective of a neuroscientist interested in Toxoplasma gondii (Nicolle et Manceaux, 1908). I reflect on the value of behavioural manipulation as a perturbation tool to understand the organisation of behaviour within the brain. Toxoplasma gondii infection reduces the aversion of rats to the olfactory cues of cat presence. This change in behaviour is one of the often-discussed exemplars of host-parasite coevolution, culminating in the manipulation of the host behaviour for the benefit of the parasite. Such coevolution also means that we can use host-parasite systems as tools to derive fundamental insights about the host brain itself.
- MeSH
- Behavior, Animal * physiology MeSH
- Host-Parasite Interactions * MeSH
- Rats MeSH
- Humans MeSH
- Toxoplasma * physiology MeSH
- Toxoplasmosis, Animal parasitology MeSH
- Toxoplasmosis parasitology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Po koupání v přírodních nádržích se v létě 2023 na několika místech v České republice objevila u lidí, zejména u dětí, cerkáriová dermatitida. Jde o imunitní reakci na průnik larvy motolice – ptačí krevničky – do kůže nesprávného hostitele. Mezi hostiteli parazita jsou plicnatí vodní plži – plovatky a okružáci – a definitivní hostitelé vodní ptáci, zejména kachny. Hodiny až dny po koupání se vyvine svědivá vyrážka, následně s puchýřky. Hojení trvá dva týdny, symptomy lze tišit antihistaminiky. Čisté vodní nádrže bez plžů jsou bezpečné a v některých přírodních nádržích po nahlášení onemocnění přistoupila samospráva nebo provozovatel koupaliště k fyzické likvidaci plžů.
After swimming in natural reservoirs in the summer of 2023, cercarial dermatitis or Swimmer's itch appeared in several places in the Czech Republic in people, especially in children. It is an immune reaction to the penetration of a fluke larva – a bird blood fluke into the skin of the wrong host. The intermediate hosts of the parasite are pulmonate aquatic gas- tropods – pond snails and ramshorns – and the definitive hosts are waterfowl, especially ducks. An itchy rash develops hours to days after bathing, followed by blisters. Healing takes two weeks symptoms can be calmed by antihistamines. Clean water reservoirs without snails are safe, and in some natural ones, after the disease has been reported, the municipality or the operator of the swimming pool proceeded to physically dispose of the snails.
- MeSH
- Cercaria * pathogenicity MeSH
- Child MeSH
- Host-Parasite Interactions MeSH
- Humans MeSH
- Skin Diseases, Parasitic * diagnosis prevention & control therapy MeSH
- Ponds MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Geographicals
- Czech Republic MeSH
Leishmania species, members of the kinetoplastid parasites, cause leishmaniasis, a neglected tropical disease, in millions of people worldwide. Leishmania has a complex life cycle with multiple developmental forms, as it cycles between a sand fly vector and a mammalian host; understanding their life cycle is critical to understanding disease spread. One of the key life cycle stages is the haptomonad form, which attaches to insect tissues through its flagellum. This adhesion, conserved across kinetoplastid parasites, is implicated in having an important function within their life cycles and hence in disease transmission. Here, we discover the kinetoplastid-insect adhesion proteins (KIAPs), which localise in the attached Leishmania flagellum. Deletion of these KIAPs impairs cell adhesion in vitro and prevents Leishmania from colonising the stomodeal valve in the sand fly, without affecting cell growth. Additionally, loss of parasite adhesion in the sand fly results in reduced physiological changes to the fly, with no observable damage of the stomodeal valve and reduced midgut swelling. These results provide important insights into a comprehensive understanding of the Leishmania life cycle, which will be critical for developing transmission-blocking strategies.
- MeSH
- Cell Adhesion MeSH
- Flagella * metabolism MeSH
- Insect Vectors parasitology MeSH
- Insect Proteins metabolism genetics MeSH
- Host-Parasite Interactions MeSH
- Leishmania * physiology genetics metabolism MeSH
- Leishmaniasis parasitology transmission MeSH
- Protozoan Proteins metabolism genetics MeSH
- Psychodidae * parasitology MeSH
- Life Cycle Stages MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
