共查询到20条相似文献,搜索用时 31 毫秒
1.
Carla M. Cabral Shraddha Tuladhar Hans K. Dietrich Elizabeth Nguyen Wes R. MacDonald Tapasya Trivedi Asha Devineni Anita A. Koshy 《PLoS pathogens》2016,12(2)
Toxoplasma gondii, a common brain-tropic parasite, is capable of infecting most nucleated cells, including astrocytes and neurons, in vitro. Yet, in vivo, Toxoplasma is primarily found in neurons. In vitro data showing that interferon-γ-stimulated astrocytes, but not neurons, clear intracellular parasites suggest that neurons alone are persistently infected in vivo because they lack the ability to clear intracellular parasites. Here we test this theory by using a novel Toxoplasma-mouse model capable of marking and tracking host cells that directly interact with parasites, even if the interaction is transient. Remarkably, we find that Toxoplasma shows a strong predilection for interacting with neurons throughout CNS infection. This predilection remains in the setting of IFN-γ depletion; infection with parasites resistant to the major mechanism by which murine astrocytes clear parasites; or when directly injecting parasites into the brain. These findings, in combination with prior work, strongly suggest that neurons are not incidentally infected, but rather they are Toxoplasma’s primary in vivo target. 相似文献
2.
Toxoplasma gondii is an obligate intracellular protozoan which infects one-third of the human population. Due to its high infection prevalence, Toxoplasma offers an ideal system for the study of host–parasite interaction. Similar to other eukaryotes, Toxoplasma maintains levels and localization of cytoplasmic mRNAs throughout its life cycle as part of a gene regulation network to meet all cellular and biochemical requirements. More recently, it was reported that the presence of cytoplasmic mRNA granules could contribute to the parasite pathogenesis and viability. Here we identified a novel Toxoplasma DEAD-box RNA helicase, referred to as Toxoplasma gondiiHomolog of DOZI (TgHoDI), because of its high homology (81%) to Plasmodium DOZI. TgHoDI is the functional ortholog of yeast DHH1, and its function was authenticated by complementation studies in Δdhh1 yeast strain. We demonstrated that TgHoDI is a marker of cytoplasmic RNA stress granules, which assemble when the parasites experience cellular stresses and translational arrest. 相似文献
3.
Thomas Mouveaux Emmanuel Roger Alioune Gueye Fanny Eysert Ludovic Huot Benjamin Grenier-Boley Jean-Charles Lambert Mathieu Gissot 《Open biology》2021,11(10)
Toxoplasma gondii is a eukaryotic parasite that forms latent cysts in the brain of immunocompetent individuals. The latent parasite infection of the immune-privileged central nervous system is linked to most complications. With no drug currently available to eliminate the latent cysts in the brain of infected hosts, the consequences of neurons'' long-term infection are unknown. It has long been known that T. gondii specifically differentiates into a latent form (bradyzoite) in neurons, but how the infected neuron responds to the infection remains to be elucidated. We have established a new in vitro model resulting in the production of mature bradyzoite cysts in brain cells. Using dual, host and parasite RNA-seq, we characterized the dynamics of differentiation of the parasite, revealing the involvement of key pathways in this process. Moreover, we identified how the infected brain cells responded to the parasite infection revealing the drastic changes that take place. We showed that neuronal-specific pathways are strongly affected, with synapse signalling being particularly affected, especially glutamatergic synapse signalling. The establishment of this new in vitro model allows investigating both the dynamics of parasite differentiation and the specific response of neurons to long-term infection by this parasite. 相似文献
4.
Fawzia H. Toulah Saedia A. Sayed Al-Ahl Dawlat M. Amin Mona H. Hamouda 《Saudi Journal of Biological Sciences》2011,18(2):151-156
Toxoplama gondii (Apicomplexa: Coccidia), an obligatory intracellular parasite with a unique capacity to invade virtually all nucleated cell type from warm-blooded vertebrate hosts. Despite the efficiency with which Toxoplasma enters its host cell, it remains unresolved if invasion occurs by direct penetration of the parasite or through phagocytosis. In the present work, electron microscopic study was designed to examine the entry process of Toxoplasma (RH strain) into macrophages and non phagocytic-host cells (Hela cells) and to observe the ultrastructure changes associated with intracellular parasitism. The results showed that both active invasion and phagocytosis were occurred and revealed that invasion is an ordered process that initiates with binding of the parasite at its apical end followed by tight-fitting invagination of the host cell membrane and a prominent constriction in the parasite at the site of penetration. The process ended by the professional parasitophorous vacuole that is distinct at the outset from those formed by phagocytosis in which once Toxoplasma triggered, phagocytic uptake can proceed by capture of the parasite within a loose fitting vacuole formed by localized membrane ruffling. The cytopathic effects of the parasite on macrophages and Hela cells were demonstrated within 5–15 h post-inoculation in the form of degenerative mitochondria, swelling Golgi apparatus and widening of endoplasmic reticulum indicating intracellular oedema. These changes were exaggerated and several cells were found dead after 48–72 h. 相似文献
5.
Aurélien Mercier Madougou Garba Henri Bonnabau Mamadou Kane Jean-Pierre Rossi Marie-Laure Dardé Gauthier Dobigny 《Memórias do Instituto Oswaldo Cruz》2013,108(4):399-407
A serological survey of Toxoplasma gondii was
conducted on 766 domestic and peridomestic rodents from 46 trapping sites
throughout the city of Niamey, Niger. A low seroprevalence was found over the
whole town with only 1.96% of the rodents found seropositive. However,
differences between species were important, ranging from less than 2% in truly
commensal Mastomys natalensis, Rattus rattus
and Mus musculus, while garden-associated Arvicanthis niloticus
displayed 9.1% of seropositive individuals. This is in line with previous
studies on tropical rodents - that we reviewed here - which altogether show that
Toxoplasma seroprevalence in rodent is highly variable,
depending on many factors such as locality and/or species. Moreover, although we
were not able to decipher statistically between habitat or species effect, such
a contrast between Nile grass rats and the other rodent species points towards a
potentially important role of environmental toxoplasmic infection. This would
deserve to be further scrutinised since intra-city irrigated cultures are
extending in Niamey, thus potentially increasing Toxoplasma
circulation in this yet semi-arid region. As far as we are aware of, our study
is one of the rare surveys of its kind performed in Sub-Saharan Africa and the
first one ever conducted in the Sahel. 相似文献
6.
Carsten G.K. Lüder Marie Chaussepied Volker T. Heussler 《International journal for parasitology》2009,39(2):163-173
The intracellular stages of apicomplexan parasites are known to extensively modify their host cells to ensure their own survival. Recently, considerable progress has been made in understanding the molecular details of these parasite-dependent effects for Plasmodium-, Toxoplasma- and Theileria-infected cells. We have begun to understand how Plasmodium liver stage parasites protect their host hepatocytes from apoptosis during parasite development and how they induce an ordered cell death at the end of the liver stage. Toxoplasma parasites are also known to regulate host cell survival pathways and it has been convincingly demonstrated that they block host cell major histocompatibility complex (MHC)-dependent antigen presentation of parasite epitopes to avoid cell-mediated immune responses. Theileria parasites are the masters of host cell modulation because their presence immortalises the infected cell. It is now accepted that multiple pathways are activated to induce Theileria-dependent host cell transformation. Although it is now known that similar host cell pathways are affected by the different parasites, the outcome for the infected cell varies considerably. Improved imaging techniques and new methods to control expression of parasite and host cell proteins will help us to analyse the molecular details of parasite-dependent host cell modifications. 相似文献
7.
Chronic infection with the intracellular protozoan parasite Toxoplasma gondii leads to tissue remodelling in the brain and a continuous requirement for peripheral leucocyte migration within the CNS (central nervous system). In the present study, we investigate the role of MMPs (matrix metalloproteinases) and their inhibitors in T-cell migration into the infected brain. Increased expression of two key molecules, MMP-8 and MMP-10, along with their inhibitor, TIMP-1 (tissue inhibitor of metalloproteinases-1), was observed in the CNS following infection. Analysis of infiltrating lymphocytes demonstrated MMP-8 and -10 production by CD4+ and CD8+ T-cells. In addition, infiltrating T-cells and CNS resident astrocytes increased their expression of TIMP-1 following infection. TIMP-1-deficient mice had a decrease in perivascular accumulation of lymphocyte populations, yet an increase in the proportion of CD4+ T-cells that had trafficked into the CNS. This was accompanied by a reduction in parasite burden in the brain. Taken together, these findings demonstrate a role for MMPs and TIMP-1 in the trafficking of lymphocytes into the CNS during chronic infection in the brain. 相似文献
8.
Jean François Dubremetz David J.P. Ferguson 《International journal for parasitology》2009,39(8):883-893
In many ways the history of the discovery of the life cycle of Toxoplasma gondii and the development of biological electron microscopy progressed in parallel through the 1950s and 1960s. Although Toxoplasma was discovered in 1908, it was only in the 1950s that the extent of the infection in humans and domestic animals was realised and work was undertaken to elucidate its life cycle (reviewed elsewhere in this edition). The development of ultrastructural techniques and their application to biological systems including Toxoplasma developed over the same period. This resulted in a synergistic effect with the re-classification of previously unrelated parasites within a single phylum, the Apicomplexa, which was based on the ultrastructural appearances of the infectious stages. This review will describe the central role played by electron microscopy and Toxoplasma in the developments associated with this progress. 相似文献
9.
Mayandi Sivaguru Glenn A. Fried Carly A. H. Miller Bruce W. Fouke 《Journal of visualized experiments : JoVE》2014,(91)
An integrated suite of imaging techniques has been applied to determine the three-dimensional (3D) morphology and cellular structure of polyp tissues comprising the Caribbean reef building corals Montastraeaannularis and M. faveolata. These approaches include fluorescence microscopy (FM), serial block face imaging (SBFI), and two-photon confocal laser scanning microscopy (TPLSM). SBFI provides deep tissue imaging after physical sectioning; it details the tissue surface texture and 3D visualization to tissue depths of more than 2 mm. Complementary FM and TPLSM yield ultra-high resolution images of tissue cellular structure. Results have: (1) identified previously unreported lobate tissue morphologies on the outer wall of individual coral polyps and (2) created the first surface maps of the 3D distribution and tissue density of chromatophores and algae-like dinoflagellate zooxanthellae endosymbionts. Spectral absorption peaks of 500 nm and 675 nm, respectively, suggest that M. annularis and M. faveolata contain similar types of chlorophyll and chromatophores. However, M. annularis and M. faveolata exhibit significant differences in the tissue density and 3D distribution of these key cellular components. This study focusing on imaging methods indicates that SBFI is extremely useful for analysis of large mm-scale samples of decalcified coral tissues. Complimentary FM and TPLSM reveal subtle submillimeter scale changes in cellular distribution and density in nondecalcified coral tissue samples. The TPLSM technique affords: (1) minimally invasive sample preparation, (2) superior optical sectioning ability, and (3) minimal light absorption and scattering, while still permitting deep tissue imaging. 相似文献
10.
Anita A. Koshy Hans K. Dietrich David A. Christian Jason H. Melehani Anjali J. Shastri Christopher A. Hunter John C. Boothroyd 《PLoS pathogens》2012,8(7)
Like many intracellular microbes, the protozoan parasite Toxoplasma gondii injects effector proteins into cells it invades. One group of these effector proteins is injected from specialized organelles called the rhoptries, which have previously been described to discharge their contents only during successful invasion of a host cell. In this report, using several reporter systems, we show that in vitro the parasite injects rhoptry proteins into cells it does not productively invade and that the rhoptry effector proteins can manipulate the uninfected cell in a similar manner to infected cells. In addition, as one of the reporter systems uses a rhoptry:Cre recombinase fusion protein, we show that in Cre-reporter mice infected with an encysting Toxoplasma-Cre strain, uninfected-injected cells, which could be derived from aborted invasion or cell-intrinsic killing after invasion, are actually more common than infected-injected cells, especially in the mouse brain, where Toxoplasma encysts and persists. This phenomenon has important implications for how Toxoplasma globally affects its host and opens a new avenue for how other intracellular microbes may similarly manipulate the host environment at large. 相似文献
11.
A Kaushansky P G Metzger A N Douglass S A Mikolajczak V Lakshmanan H S Kain S HI Kappe 《Cell death & disease》2013,4(8):e762
Intracellular eukaryotic parasites and their host cells constitute complex, coevolved cellular interaction systems that frequently cause disease. Among them, Plasmodium parasites cause a significant health burden in humans, killing up to one million people annually. To succeed in the mammalian host after transmission by mosquitoes, Plasmodium parasites must complete intracellular replication within hepatocytes and then release new infectious forms into the blood. Using Plasmodium yoelii rodent malaria parasites, we show that some liver stage (LS)-infected hepatocytes undergo apoptosis without external triggers, but the majority of infected cells do not, and can also resist Fas-mediated apoptosis. In contrast, apoptosis is dramatically increased in hepatocytes infected with attenuated parasites. Furthermore, we find that blocking total or mitochondria-initiated host cell apoptosis increases LS parasite burden in mice, suggesting that an anti-apoptotic host environment fosters parasite survival. Strikingly, although LS infection confers strong resistance to extrinsic host hepatocyte apoptosis, infected hepatocytes lose their ability to resist apoptosis when anti-apoptotic mitochondrial proteins are inhibited. This is demonstrated by our finding that B-cell lymphoma 2 family inhibitors preferentially induce apoptosis in LS-infected hepatocytes and significantly reduce LS parasite burden in mice. Thus, targeting critical points of susceptibility in the LS-infected host cell might provide new avenues for malaria prophylaxis. 相似文献
12.
Background
The parasite Toxoplasma gondii influences the behaviour of infected animals and probably also personality of infected humans. Subjects with a Rhesus-positive blood group are protected against certain behavioural effects associated with Toxoplasma infection, including the deterioration of reaction times and personality factor shift.Methodology/Principal Findings
Here, we searched for differences in the toxoplasmosis-associated effects between RhD-positive and RhD-negative subjects by testing 502 soldiers with two personality tests and two intelligence tests. The infected subjects expressed lower levels of all potentially pathognomic factors measured with the N-70 questionnaire and in neurasthenia measured with NEO-PI-R. The RhD-positive, Toxoplasma-infected subjects expressed lower while RhD-negative, Toxoplasma-infected subjects expressed higher intelligence than their Toxoplasma-free peers. The observed Toxoplasma-associated differences were always larger in RhD-negative than in RhD-positive subjects.Conclusions
RhD phenotype plays an important role in the strength and direction of association between latent toxoplasmosis and not only psychomotor performance, but also personality and intelligence. 相似文献13.
Schizophrenia is a serious neuropsychiatric disease of uncertain etiology, which causes human mental disorder and affects about 1% of the population. In recently years, some studies showed that some cases of schizophrenia may be associated with Toxoplasma gondii infection. In order to investigate a potential association between Toxoplasma infection and schizophrenia, we investigated the relative clinical symptom of schizophrenia such as learning and memory capability, depression and stereotypy to find some useful information by behavioral test in mouse models. Our results demonstrated that mice from Toxoplasma infection and MK-801 administration (as the model of schizophrenia) were impaired in learning and memory capability, and they had more serious depression and stereotypy compared with the control mice, especially the mice from congenital Toxoplasma infection. In addition, our results clearly showed that the number of cysts in brain tissue of congenital Toxoplasma infection mice was significantly low than in acquired Toxoplasma infected mice. Collectively, these results suggested a potential association between Toxoplasma infection and schizophrenia. 相似文献
14.
Toxoplasmosis, a neglected tropical disease caused by the protozoan parasite Toxoplasma gondii, occurs throughout the world. Human T. gondii infection is asymptomatic in 80% of the population; however, the infection is life-threatening and causes substantial neurologic damage in immunocompromised patients such as HIV-infected persons. The major purpose of this study was to investigate the seroprevalence of T. gondii infection in subjects infected with HIV/AIDS in eastern China. Our findings showed 9.7% prevalence of anti-T. gondii IgG antibody in HIV/AIDS patients, which was higher than in intravenous drug users (2.2%) and healthy controls (4.7%), while no significant difference was observed in the seroprevalence of anti-Toxoplasma IgM antibody among all participants (P>0.05). Among all HIV/AIDS patients, 15 men (7.7%) and 10 women (15.9%) were positive for anti-T. gondii IgG antibody; however, no significant difference was detected in the seroprevalence of anti-Toxoplasma IgG antibody between males and females. The frequency of anti-Toxoplasma IgG antibody was 8.0%, 13.2%, 5.5%, and 0% in patients with normal immune function (CD4+ T-lymphocyte count ≥500 cells/ml), immunocompromised patients (cell count ≥200 and <500 cells/ml), severely immunocompromised patients (cell count ≥50 and <200 cells/ml), and advanced AIDS patients, respectively (cell count <50 cells/ml), while only 3 immunocompromised patients were positive for anti-T. gondii IgM antibody. The results indicate a high seroprevalence of T. gondii infection in HIV/AIDS patients in eastern China, and a preventive therapy for toxoplasmosis may be given to HIV/AIDS patients based on CD4+ T lymphocyte count. 相似文献
15.
A method is described for obtaining maximum yield of Toxoplasma tachyzoites from the peritoneal cavity of infected mice. Mice injected with 102 parasites contain more Toxoplasma in this site at the time of death than mice injected with larger numbers. The host does not mount a detectable humoral response to the parasite. 相似文献
16.
Belinda J. Morahan Georgina B. Sallmann Valentina Dubljevic 《Experimental parasitology》2009,122(4):280-288
The Apicomplexan parasites Toxoplasma and Plasmodium, respectively, cause toxoplasmosis and malaria in humans and although they invade different host cells they share largely conserved invasion mechanisms. Plasmodium falciparum merozoite invasion of red blood cells results from a series of co-ordinated events that comprise attachment of the merozoite, its re-orientation, release of the contents of the invasion-related apical organelles (the rhoptries and micronemes) followed by active propulsion of the merozoite into the cell via an actin-myosin motor. During this process, a tight junction between the parasite and red blood cell plasma membranes is formed and recent studies have identified rhoptry neck proteins, including PfRON4, that are specifically associated with the tight junction during invasion. Here, we report the structure of the gene that encodes PfRON4 and its apparent limited diversity amongst geographically diverse P. falciparum isolates. We also report that PfRON4 protein sequences elicit immunogenic responses in natural human malaria infections. 相似文献
17.
Ailan F Arenas Gladys E Salcedo Diego M Moncada Diego A Erazo Juan F Osorio Jorge E Gomez-Marin 《Bioinformation》2012,8(19):916-923
Toxoplasma gondii invade host cells using a multi-step process that depends on the regulated secretion of adhesions. To identify key
primary sequence features of adhesins in this parasite, we analyze the relative frequency of individual amino acids, their dipeptide
frequencies, and the polarity, polarizability and Van der Waals volume of the individual amino acids by using cluster analysis. This
method identified cysteine as a key amino acid in the Toxoplasma adhesin group. The best vector algorithm of non-concatenated
features was for 2 attributes: the single amino acid relative frequency and the dipeptide frequency. Polarity, polarizability and Van
der Waals volume were not good classificatory attributes. Single amino acid attributes clustered unambiguously 67 apicomplexan
hypothetical adhesins. This algorithm was also useful for clustering hypothetical Toxoplasma target host receptors. All of the cluster
performances had over 70% sensitivity and 80% specificity. Compositional aminoacid data can be useful for improving machine
learning-based prediction software when homology and structural data are not sufficient. 相似文献
18.