共查询到20条相似文献,搜索用时 15 毫秒
1.
2.
Annina Bindschedler Rahel Wacker Jessica Egli Nina Eickel Jacqueline Schmuckli‐Maurer Blandine M. Franke‐Fayard Chris J. Janse Volker T. Heussler 《Cellular microbiology》2021,23(1)
The protozoan parasite Plasmodium, causative agent of malaria, invades hepatocytes by invaginating the host cell plasma membrane and forming a parasitophorous vacuole membrane (PVM). Surrounded by this PVM, the parasite undergoes extensive replication. Parasites inside a PVM provoke the Plasmodium‐associated autophagy‐related (PAAR) response. This is characterised by a long‐lasting association of the autophagy marker protein LC3 with the PVM, which is not preceded by phosphatidylinositol 3‐phosphate (PI3P)‐labelling. Prior to productive invasion, sporozoites transmigrate several cells and here we describe that a proportion of traversing sporozoites become trapped in a transient traversal vacuole, provoking a host cell response that clearly differs from the PAAR response. These trapped sporozoites provoke PI3P‐labelling of the surrounding vacuolar membrane immediately after cell entry, followed by transient LC3‐labelling and elimination of the parasite by lysosomal acidification. Our data suggest that this PI3P response is not only restricted to sporozoites trapped during transmigration but also affects invaded parasites residing in a compromised vacuole. Thus, host cells can employ a pathway distinct from the previously described PAAR response to efficiently recognise and eliminate Plasmodium parasites. 相似文献
3.
《Cell reports》2023,42(7):112727
- Download : Download high-res image (202KB)
- Download : Download full-size image
4.
5.
M Lopes da Silva C Thieleke-Matos L Cabrita-Santos JS Ramalho ST Wavre-Shapton CE Futter DC Barral MC Seabra 《Traffic (Copenhagen, Denmark)》2012,13(10):1351-1363
The obligate intracellular liver stage of the Plasmodium parasite represents a bottleneck in the parasite life cycle and remains a promising target for therapeutic intervention. During this stage, parasites undergo dramatic morphological changes and achieve one of the fastest replication rates among eukaryotic species. Nevertheless, relatively little is known about the parasite interactions with the host hepatocyte. Using immunofluorescence, live cell imaging and electron microscopy, we show that Plasmodium berghei parasites are surrounded by vesicles from the host late endocytic pathway. We found that these vesicles are acidic and contain the membrane markers Rab7a, CD63 and LAMP1. When host cell vesicle acidification was disrupted using ammonium chloride or Concanamycin A during the late liver stage of infection, parasite survival was not affected, but schizont size was significantly decreased. Furthermore, when the host cell endocytic pathway was loaded with BSA-gold, gold particles were found within the parasite cytoplasm, showing the transport of material from the host endocytic pathway toward the parasite interior. These observations reveal a novel Plasmodium-host interaction and suggest that vesicles from the host endolysosomal pathway could represent an important source of nutrients exploited by the fast-growing late liver stage parasites. 相似文献
6.
7.
8.
Carolina Thieleke‐Matos Mafalda Lopes da Silva Laura Cabrita‐Santos Cristiana F. Pires José S. Ramalho Ognian Ikonomov Elsa Seixas Assia Shisheva Miguel C. Seabra Duarte C. Barral 《Traffic (Copenhagen, Denmark)》2014,15(10):1066-1082
Malaria parasites go through an obligatory liver stage before they infect erythrocytes and cause disease symptoms. In the host hepatocytes, the parasite is enclosed by a parasitophorous vacuole membrane (PVM). Here, we dissected the interaction between the Plasmodium parasite and the host cell late endocytic pathway and show that parasite growth is dependent on the phosphoinositide 5‐kinase (PIKfyve) that converts phosphatidylinositol 3‐phosphate [PI(3)P] into phosphatidylinositol 3,5‐bisphosphate [PI(3,5)P2] in the endosomal system. We found that inhibition of PIKfyve by either pharmacological or non‐pharmacological means causes a delay in parasite growth. Moreover, we show that the PI(3,5)P2 effector protein TRPML1 that is involved in late endocytic membrane fusion, is present in vesicles closely contacting the PVM and is necessary for parasite growth. Thus, our studies suggest that the parasite PVM is able to fuse with host late endocytic vesicles in a PI(3,5)P2‐dependent manner, allowing the exchange of material between the host and the parasite, which is essential for successful infection. 相似文献
9.
Josephine Grützke Kerstin Rindte Christian Goosmann Olivier Silvie Carolin Rauch Dagmar Heuer Maik J Lehmann Ann‐Kristin Mueller Volker Brinkmann Kai Matuschewski Alyssa Ingmundson 《Traffic (Copenhagen, Denmark)》2014,15(4):362-382
For membrane‐bound intracellular pathogens, the surrounding vacuole is the portal of communication with the host cell. The parasitophorous vacuole (PV) harboring intrahepatocytic Plasmodium parasites satisfies the parasites' needs of nutrition and protection from host defenses to allow the rapid parasite growth that occurs during the liver stage of infection. In this study, we visualized the PV membrane (PVM) and the associated tubovesicular network (TVN) through fluorescent tagging of two PVM‐resident Plasmodium berghei proteins, UIS4 and IBIS1. This strategy revealed previously unrecognized dynamics with which these membranes extend throughout the host cell. We observed dynamic vesicles, elongated clusters of membranes and long tubules that rapidly extend and contract from the PVM in a microtubule‐dependent manner. Live microscopy, correlative light‐electron microscopy and fluorescent recovery after photobleaching enabled a detailed characterization of these membranous features, including velocities, the distribution of UIS4 and IBIS1, and the connectivity of PVM and TVN. Labeling of host cell compartments revealed association of late endosomes and lysosomes with the elongated membrane clusters. Moreover, the signature host autophagosome protein LC3 was recruited to the PVM and TVN and colocalized with UIS4. Together, our data demonstrate that the membranes surrounding intrahepatic Plasmodium are involved in active remodeling of host cells. 相似文献
10.
Lee HW Moon SU Ryu HS Kim YJ Cho SH Chung GT Lin K Na BK Kong Y Chung KS Kim TS 《The Korean journal of parasitology》2006,44(1):49-54
In order to develop tools for an early serodiagnosis of Plasmodium falciparum infection, we evaluated the usefulness of P. falciparum liver stage antigen-3 (LSA-3) as a serodiagnostic antigen. A portion of LSA-3 gene was cloned, and its recombinant protein (rLSA-3) was expressed in Escherichia coli and purified by column chromatography. The purified rLSA-3 and 120 test blood/serum samples collected from inhabitants in malaria-endemic areas of Mandalay, Myanmar were used for this study. In microscopic examinations of blood samples, P. falciparum positive rate was 39.1% (47/120) in thin smear trials, and 33.3% (40/120) in thick smear trials. Although the positive rate associated with the rLSA-3 (30.8%) was lower than that of the blood stage antigens (70.8%), rLSA-3 based enzyme-linked immunosorbent assay could detect 12 seropositive cases (10.0%), in which blood stage antigens were not detected. These results indicate that the LSA-3 is a useful antigen for an early serodiagnosis of P. falciparum infection. 相似文献
11.
Lee HW Moon SU Kim YJ Cho SH Lin K Na BK Kim TS 《The Korean journal of parasitology》2008,46(3):195-198
Plasmodium falciparum liver stage antigen-1 (PfLSA-1) is one of the few antigens expressed exclusively in liver stage parasites. In this study, we evaluated the antibody responses against recombinant PfLSA-1 in naturally infected individuals in Myanmar. High levels of antibody responses (70.7%) were detected in 82 serum samples from 116 infected individuals, and IgG responses to PfLSA-1 principally composed of responses of IgG1 and IgG3 subclasses. These results show that PfLSA-1 elicits effective antibody responses in individuals infected with P. falciparum, and thus it could be not only an attractive candidate protein for vaccine development, but also a useful antigen for serodiagnosis of the infection. 相似文献
12.
13.
The ABSCISIC ACID-INSENSITIVE 3 (ABI3) gene is expressed during vegetative quiescence processes in Arabidopsis 总被引:2,自引:0,他引:2
The ABSCISIC ACID-INSENSITIVE 3 ( ABI3 ) gene of Arabidopsis thaliana (L.) Heynh is known to play an important role during seed maturation and dormancy. Here, we present evidence suggesting an additional role for ABI3 during vegetative quiescence processes. During growth in the dark, ABI3 is expressed in the apex of the seedlings after cell division is arrested. The 2S seed storage protein gene, a target gene of ABI3 in seeds, is also induced in the arrested apex under similar darkness conditions. In addition, β -glucuronidase expression under the control of the ABI3 promoter is abolished by treatments that provoke leaf development in the dark [sucrose and abscisic acid (ABA) biosynthesis inhibitors] and induced by treatments that prevent leaf development (darkness and ABA). Furthermore, ABI3 expression is absent in apices of dark-grown de-etiolated ( det 1 ) and abi3 mutants, both known to develop leaves or leaf primordia in the dark. The fact that the expression of the ABI3 gene is only observed in a fraction of the analysed plants suggests that ABI3 is probably only one of the components of a molecular network underlying quiescence. In addition to the expression of ABI3 in apices of dark-grown seedlings, the ABI3 promoter confers expression in other vegetative organs as well, such as the stipules and the abscission zones of the siliques. In conclusion, apart from its role in seed development, ABI3 might have additional functions. 相似文献
14.
Ya Gong Mathieu Danoy Taketomo Kido Kento Mitsuhashi Hyunjin Choi Tomoaki Matsugi Jingjing Yang Katsuhiro Esashika Jun Takahashi Masaki Nishikawa Taichi Ito Atsushi Miyajima Yasuyuki Sakai 《Biotechnology and bioengineering》2023,120(8):2345-2356
Hepatic stellate cells (HSCs) play a crucial role in liver fibrosis by producing excessive extracellular matrix (ECM) following chronic inflammation. However, studying HSC function has been challenging due to the limited availability of primary human quiescent HSCs (qHSCs) in vitro, and the fact that primary qHSCs quickly activate when cultured on plastic plates. Advances in stem cell technology have allowed for the generation of qHSCs from human induced pluripotent stem cells (hiPSCs) with the potential to provide an unlimited source of cells. However, differentiated quiescent-like HSCs (iqHSCs) also activate spontaneously on conventional plastic plates. In this study, we generated iqHSCs from hiPSCs and developed a culture method to maintain such iqHSCs in a lowly activated state for up to 5 days by optimizing their physical culture microenvironment. We observed that three-dimensional (3D) culture of iqHSCs in soft type 1 collagen hydrogels significantly inhibited their spontaneous activation in vitro while maintaining their ability to convert to activated state. Activation of iqHSC was successfully modeled by stimulating them with the fibrotic cytokine TGFβ1. Hence, our culture method can be used to generate HSCs with functions comparable to those in a healthy liver, facilitating the development of accurate in vitro liver models for identifying novel therapeutic agents. 相似文献
15.
探讨Listr1遗传位点影响小鼠对疟原虫易感性的可能性及其初步作用机制。致死型约氏疟原虫(Plasmodiumyoelii17XL,P.y17XL)感染C.B6By-Listr1小鼠(BALB/c小鼠基因背景下引入C57BL/6小鼠Lis-tr1遗传位点的同类系小鼠)和BALB/c小鼠,分析二者生存率和感染率的差异;HE染色分析P.y17XL感染后第5天C.B6By-Listr1小鼠和BALB/c小鼠肝脏组织损伤情况;定量PCR法检测P.y17XL感染后小鼠肝脏组织第1、2、5天IL-1β、IL-6、TNF-α、IFN-γ的表达含量。结果显示,P.y17XL感染后4~8dC.B6By-Listr1小鼠虫血症水平显著高于BALB/c小鼠(P<0.05)。C.B6By-Listr1小鼠于感染后7~9d全部死亡;而半数BALB/c小鼠于感染后8~9d死亡,其余BALB/c小鼠至感染后第13天仍存活,两种小鼠生存率差异具有统计学意义(P<0.01)。C.B6By-Listr1小鼠P.y17XL感染后第5天肝组织HE染色可见到明显的疟色素沉积;而BALB/c小鼠全片基本未见到疟色素的沉积。P.y17XL感染后第2天BALB/c小鼠肝组织IL-6(P<0.05)、TNF-α(P<0.05)mRNA水平显著高于C.B6By-Listr1小鼠。结果表明Listr1遗传位点可以影响小鼠对疟原虫的易感性,与肝脏固有免疫相关。 相似文献
16.
A tightly controlled balance between hematopoietic stem and progenitor cell compartments is required to maintain normal blood cell homeostasis throughout life, and this balance is regulated by intrinsic and extrinsic cellular factors. Cav-1 is a 22-kDa protein that is located in plasma membrane invaginations and is implicated in regulating neural stem cell and embryonic stem cell proliferation. However, the role of Cav-1 in hematopoietic stem cell (HSC) function is largely unknown. In this study, we used Cav-1−/− mice to investigate the role of Cav-1 in HSCs function during aging. The results showed that Cav-1−/− mice displayed a decreased percentage of B cells and an increased percentage of M cells in the bone marrow and peripheral blood, and these changes were due to an increased number of HSCs. FACS analysis showed that the numbers of Lin−Sca1+c-kit+ cells (LSKs), long-term HSCs (LT-HSCs), short-term HSCs and multipotent progenitors were increased in Cav-1−/− mice compared with Cav-1+/+ mice, and this increase became more pronounced with aging. An in vitro clonogenic assay showed that LT-HSCs from Cav-1−/− mice had reduced ability to self-renew. Consistently, an in vivo competitive transplantation assay showed that Cav-1−/− mice failed to reconstitute hematopoiesis. Moreover, a Cav-1 deletion disrupted the quiescence of LSKs and promoted cell cycle progression through G2/M phase. In addition, we found that Cav-1 deletion impaired the ability of HSCs to differentiate into mature blood cells. Taken together, these data suggest that Cav-1-deficient cells impaired HSCs quiescence and induced environmental alterations, which limited HSCs self-renewal and function. 相似文献
17.
《Bioorganic & medicinal chemistry letters》2014,24(17):4151-4157
The malaria parasite Plasmodium goes through two life stages in the human host, a non-symptomatic liver stage (LS) followed by a blood stage with all clinical manifestation of the disease. In this study, we investigated a series of 2-alkynoic fatty acids (2-AFAs) with chain lengths between 14 and 18 carbon atoms for dual in vitro activity against both life stages. 2-Octadecynoic acid (2-ODA) was identified as the best inhibitor of Plasmodium berghei parasites with ten times higher potency (IC50 = 0.34 μg/ml) than the control drug. In target determination studies, the same compound inhibited three Plasmodium falciparum FAS-II (PfFAS-II) elongation enzymes PfFabI, PfFabZ, and PfFabG with the lowest IC50 values (0.28–0.80 μg/ml, respectively). Molecular modeling studies provided insights into the molecular aspects underlying the inhibitory activity of this series of 2-AFAs and a likely explanation for the considerably different inhibition potentials. Blood stages of P. falciparum followed a similar trend where 2-ODA emerged as the most active compound, with 20 times less potency. The general toxicity and hepatotoxicity of 2-AFAs were evaluated by in vitro and in vivo methods in mammalian cell lines and zebrafish models, respectively. This study identifies 2-ODA as the most promising antiparasitic 2-AFA, particularly towards P. berghei parasites. 相似文献
18.
A natural infestation of Meloidogyne javanica in an aggregated Oxisol declined at an exponential rate when aliquots of the soil were stored for 72 days in polyethylene bags at various soil water potentials (Ψ). Time periods required for reduction in soil infestations by 50% were 2.7, 4.9, 110, 10, and 2.6 days at Ψ of -0.16, -0.30, -1.1, -15, and -92 bars, respectively. In the wetter soils, at Ψ of -0.16, -0.30, and -1.1 bars, the predominant stage recovered was the second-stage larva. In the drier soils, at Ψ of -15 and -92 bars, both eggs and larvae were recovered with neither stage predominating. Incidence of coiled larvae was inversely related to the Ψ value of the soil, a greater incidence occurring in the drier soils. After 15-32 days, percentages of coiled larvae were 13, 27, 55, 65, and 88% in soil at Ψ of -0.17, -0.60, -1.9, -15, and -82 bars, respectively. 相似文献
19.
MARK F. WISER 《The Journal of eukaryotic microbiology》1995,42(6):659-664
ABSTRACT. Protein phosphorylation events may play important roles in the replication and differentiation of the malarial parasite. Investigations into the lability of a Plasmodium protein kinase revealed that a 34 kDa parasite phosphoprotein is rapidly converted into a 19 kDa fragment. Coincident with this conversion is a nearly total loss of a protein kinase activity, as determined from the phosphorylation of endogenous protein substrates. Both the conversion of the 34 kDa protein to the 19 kDa protein and the loss of protein kinase activity are inhibited by thio-protease inhibitors. The presence of low levels of the intact 34 kDa protein restores the protein kinase activity to almost maximum levels. However, it was not possible to demonstrate protein kinase activity associated with the 34 kDa protein, thus suggesting that the 34 kDa protein is probably an activator or regulator of the protein kinase activity and not a protein kinase. The conversion to the 19 kDa fragment also occurs in vivo and only during the schizont stage prior to the appearance of ring forms. During this same period the protein kinase activity decreases suggesting that the proteolytic processing of the 34 kDa protein may be a physiological regulator of the protein kinase. 相似文献
20.
O'Farrell PH 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2011,366(1584):3498-3507
Cell cycle investigations have focused on relentless exponential proliferation of cells, an unsustainable situation in nature. Proliferation of cells, whether microbial or metazoan, is interrupted by periods of quiescence. The vast majority of cells in an adult metazoan lie quiescent. As disruptions in this quiescence are at the foundation of cancer, it will be important for the field to turn its attention to the mechanisms regulating quiescence. While often presented as a single topic, there are multiple forms of quiescence each with complex inputs, some of which are tied to conceptually challenging aspects of metazoan regulation such as size control. In an effort to expose the enormity of the challenge, I describe the differing biological purposes of quiescence, and the coupling of quiescence in metazoans to growth and to the structuring of tissues during development. I emphasize studies in the organism rather than in tissue culture, because these expose the diversity of regulation. While quiescence is likely to be a primitive biological process, it appears that in adapting quiescence to its many distinct biological settings, evolution has diversified it. Consideration of quiescence in different models gives us an overview of this diversity. 相似文献