Cellular and immunological basis of the host-parasite relationship during infection withNeospora caninum

Parasitology ◽  
2006 ◽  
Vol 133 (3) ◽  
pp. 261-278 ◽  
Author(s):  
A. HEMPHILL ◽  
N. VONLAUFEN ◽  
A. NAGULESWARAN
Keyword(s):  
Host Cell ◽  
Cell Biology ◽  
Neospora Caninum ◽  
Host Cells ◽  
Term Survival ◽  
Prevention Of Infection ◽  
Parasite Relationship ◽  
Potential Applications

Neospora caninumis an apicomplexan parasite that is closely related toToxoplasma gondii, the causative agent of toxoplasmosis in humans and domestic animals. However, in contrast toT. gondii, N. caninumrepresents a major cause of abortion in cattle, pointing towards distinct differences in the biology of these two species. There are 3 distinct key features that represent potential targets for prevention of infection or intervention against disease caused byN. caninum. Firstly, tachyzoites are capable of infecting a large variety of host cellsin vitroandin vivo. Secondly, the parasite exploits its ability to respond to alterations in living conditions by converting into another stage (tachyzoite-to-bradyzoite orvice versa). Thirdly, by analogy withT. gondii, this parasite has evolved mechanisms that modulate its host cells according to its own requirements, and these must, especially in the case of the bradyzoite stage, involve mechanisms that ensure long-term survival of not only the parasite but also of the host cell. In order to elucidate the molecular and cellular bases of these important features ofN. caninum, cell culture-based approaches and laboratory animal models are being exploited. In this review, we will summarize the current achievements related to host cell and parasite cell biology, and will discuss potential applications for prevention of infection and/or disease by reviewing corresponding work performed in murine laboratory infection models and in cattle.

Neospora caninum and neosporosis — recent achievements in host and parasite cell biology and treatment

2006 ◽  
Vol 51 (1) ◽  
Author(s):  
Andrew Hemphill ◽  
Bruno Gottstein
Keyword(s):  
Life Cycle ◽  
Host Cell ◽  
Cell Biology ◽  
Neospora Caninum ◽  
Host Cells ◽  
Term Survival ◽  
Parasite Cell ◽  
Invasion Stage

AbstractNeospora caninum is an apicomplexan parasite, which owes its importance to the fact that it represents the major infectious cause of bovine abortion worldwide. Its life cycle is comprised of three distinct stages: Tachyzoites, representing the proliferative and disease-causing stage, bradyzoites, representing a slowly replicating, tissue cyst-forming stage, and sporozoites, which represent the end product of a sexual process taking place within the intestinal tissue of the final canine host. Tachyzoites are capable of infecting a large variety of host cells in vitro and in vivo, while bradyzoites have been found mainly within the central nervous system. In order to survive, proliferate, and proceed in its life cycle, N. caninum has evolved some amazing features. First, the parasite profits immensely from its ability to interact with, and invade, a large number of host cell types. Secondly, N. caninum exploits its capability to respond to alterations in living conditions by converting into another stage (tachyzoite-to-bradyzoite or vice versa). Thirdly, this parasite has evolved mechanisms that modulate its host cells according to its own requirements, and these must, especially in the case of the bradyzoite stage, involve mechanisms that ensure long term survival of not only the parasite but also of the host cell. These three key events (host cell invasion — stage conversion — host cell modulation) represent potential targets for intervention. In order to elucidate the molecular and cellular bases of these important features of N. caninum, cell culture-based approaches and laboratory animal models are extensively exploited. In this review, we will summarize the present knowledge and achievements related to host cell and parasite cell biology.

scholarly journals Complementation of the fadA Mutation in Fusobacterium nucleatum Demonstrates that the Surface-Exposed Adhesin Promotes Cellular Invasion and Placental Colonization

2009 ◽  
Vol 77 (7) ◽  
pp. 3075-3079 ◽  
Author(s):  
Akihiko Ikegami ◽  
Peter Chung ◽  
Yiping W. Han
Keyword(s):  
Host Cell ◽  
Cell Attachment ◽  
Adverse Pregnancy Outcome ◽  
Fusobacterium Nucleatum ◽  
Host Cells ◽  
Mouse Placenta ◽  
Host Cell Attachment ◽  
Adverse Pregnancy

ABSTRACT Fusobacterium nucleatum is a gram-negative oral anaerobe implicated in periodontal disease and adverse pregnancy outcome. The organism colonizes the mouse placenta, causing localized infection and inflammation. The mechanism of placental colonization has not been elucidated. Previous studies identified a novel adhesin from F. nucleatum, FadA, as being involved in the attachment and invasion of host cells. The fadA deletion mutant F. nucleatum 12230 US1 was defective in host cell attachment and invasion in vitro, but it also exhibited pleiotropic effects with altered cell morphology and growth rate. In this study, a fadA-complementing clone, F. nucleatum 12230 USF81, was constructed. The expression of FadA on USF81 was confirmed by Western blotting and immunofluorescent labeling. USF81 restored host cell attachment and invasion activities. The ability of F. nucleatum 12230, US1, and USF81 to colonize the mouse placenta was examined. US1 was severely defective in placental colonization compared to the wild type and USF81. Thus, FadA plays an important role in F. nucleatum colonization in vivo. These results also represent the first complementation studies for F. nucleatum. FadA may be a therapeutic target for preventing F. nucleatum colonization of the host.

scholarly journals Molecular cloning and characterization ofNcROP2Fam-1, a member of the ROP2 family of rhoptry proteins inNeospora caninumthat is targeted by antibodies neutralizing host cell invasionin vitro

Parasitology ◽  
2013 ◽  
Vol 140 (8) ◽  
pp. 1033-1050 ◽  
Author(s):  
FERIAL ALAEDDINE ◽  
ANDREW HEMPHILL ◽  
KARIM DEBACHE ◽  
CHRISTOPHE GUIONAUD
Keyword(s):  
Host Cell ◽  
Family Member ◽  
Vaccine Candidate ◽  
Neospora Caninum ◽  
Parasitophorous Vacuole ◽  
Host Cells ◽  
General Belief ◽  
Intracellular Parasites ◽  
Promising Vaccine Candidate

SUMMARYRecent publications demonstrated that a fragment of aNeospora caninumROP2 family member antigen represents a promising vaccine candidate. We here report on the cloning of the cDNA encoding this protein,N. caninumROP2 family member 1 (NcROP2Fam-1), its molecular characterization and localization. The protein possesses the hallmarks of ROP2 family members and is apparently devoid of catalytic activity. NcROP2Fam-1 is synthesized as a pre-pro-protein that is matured to 2 proteins of 49 and 55 kDa that localize to rhoptry bulbs. Upon invasion the protein is associated with the nascent parasitophorous vacuole membrane (PVM), evacuoles surrounding the host cell nucleus and, in some instances, the surface of intracellular parasites. Staining was also observed within the cyst wall of ‘cysts’ producedin vitro. Interestingly, NcROP2Fam-1 was also detected on the surface of extracellular parasites entering the host cells and antibodies directed against NcROP2Fam-1-specific peptides partially neutralized invasionin vitro. We conclude that, in spite of the general belief that ROP2 family proteins are intracellular antigens, NcROP2Fam-1 can also be considered as an extracellular antigen, a property that should be taken into account in further experiments employing ROP2 family proteins as vaccines.

Tissue Culture and Explant Approaches to Studying and VisualizingNeospora caninumand Its Interactions with the Host Cell

2004 ◽  
Vol 10 (5) ◽  
pp. 602-620 ◽  
Author(s):  
Andrew Hemphill ◽  
Nathalie Vonlaufen ◽  
Arunasalam Naguleswaran ◽  
Nadine Keller ◽  
Michele Riesen ◽  
...  
Keyword(s):  
Tissue Culture ◽  
Host Cell ◽  
Neospora Caninum ◽  
Final Host ◽  
Host Cells ◽  
Mammalian Host ◽  
Molecular Characteristics ◽  
Culture Models ◽  
Cerebral Infection

Neospora caninumis an apicomplexan parasite first mentioned in 1984 as a causative agent of neuromuscular disease in dogs. It is closely related toToxoplasma gondiiandHammondia heydorni, and its subsequent description in 1988 has been, and still is, accompanied by discussions on the true phylogenetical status of the genusNeospora.N. caninumexhibits features that clearly distinguish this parasite from other members of the Apicomplexa, including distinct ultrastructural properties, genetic background, antigenic composition, host cell interactions, and the definition of the dog as a final host. Most importantly,N. caninumhas a particular significance as a cause of abortion in cattle.In vitroculture has been indispensable for the isolation of this parasite and for investigations on the ultrastructural, cellular, and molecular characteristics of the different stages ofN. caninum. Tissue culture systems include maintenance ofN. caninumtachyzoites, which represent the rapidly proliferating stage in a large number of mammalian host cells, culture of parasites in organotypic brain slice cultures as a tool to investigate cerebral infection byN. caninum, and the use of techniques to induce the stage conversion from the tachyzoite stage to the slowly proliferating and tissue cyst-forming bradyzoite stage. This review will focus on the use of these tissue culture models as well as light- and electron-microscopical techniques for studies onN. caninumtachyzoites and bradyzoites, and on the physical interactions between parasites and host cells.

scholarly journals Division of the Salmonella-Containing Vacuole and Depletion of Acidic Lysosomes in Salmonella-Infected Host Cells Are Novel Strategies of Salmonella enterica To Avoid Lysosomes

2009 ◽  
Vol 78 (1) ◽  
pp. 68-79 ◽  
Author(s):  
Sandeepa M. Eswarappa ◽  
Vidya Devi Negi ◽  
Sangeeta Chakraborty ◽  
B. K. Chandrasekhar Sagar ◽  
Dipshikha Chakravortty
Keyword(s):  
Infected Cell ◽  
Host Cell ◽  
Salmonella Enterica ◽  
Host Cells ◽  
Infected Host ◽  
Nitrogen Species ◽  
Lysosomal Degradation ◽  
Infected Host Cell

ABSTRACT Salmonella has evolved several strategies to counteract intracellular microbicidal agents like reactive oxygen and nitrogen species. However, it is not yet clear how Salmonella escapes lysosomal degradation. Some studies have demonstrated that Salmonella can inhibit phagolysosomal fusion, whereas other reports have shown that the Salmonella-containing vacuole (SCV) fuses/interacts with lysosomes. Here, we have addressed this issue from a different perspective by investigating if the infected host cell has a sufficient quantity of lysosomes to target Salmonella. Our results suggest that SCVs divide along with Salmonella, resulting in a single bacterium per SCV. As a consequence, the SCV load per cell increases with the division of Salmonella inside the host cell. This demands more investment from the host cell to counteract Salmonella. Interestingly, we observed that Salmonella infection decreases the number of acidic lysosomes inside the host cell both in vitro and in vivo. These events potentially result in a condition in which an infected cell is left with insufficient acidic lysosomes to target the increasing number of SCVs, which favors the survival and proliferation of Salmonella inside the host cell.

Interactions between mosses (Bryophyta) and fungi

2006 ◽  
Vol 84 (10) ◽  
pp. 1509-1519 ◽  
Author(s):  
Marie L. Davey ◽  
Randolph S. Currah
Keyword(s):  
Host Cell ◽  
Mycorrhizal Fungi ◽  
Host Responses ◽  
Fungal Propagules ◽  
Parasite Relationship ◽  
Cellular Specificity ◽  
Host Parasite ◽  
Highly Evolved

A taxonomically diverse suite of fungi interacts with bryophytes as pathogens, parasites, saprobes, and commensals. Necrotrophic pathogens such as Tephrocybe palustris (Peck) Donk and Nectria mnii Döbbeler form patches of moribund gametophytes in otherwise healthy mats of mosses. These pathogens exhibit different methods of host cell disruption; N. mnii appears to displace the host cell protoplast with intracellular hyphae, while T. palustris causes host protoplast degeneration. Host responses to infection by bryopathogens are also variable. Host–pathogen relationships can be highly evolved, as in Bryophytomyces sphagni (Navashin) Cif., in which fungal propagules replace the bryophyte spores, and exploit the explosive dispersal mechanisms of the Sphagnum host. Bryophilous parasites tend to exhibit high tissue or cellular specificity with varying host specificity. For example, Octospora similis (Kirchstein) Benkert infects the rhizoids of species of Bryum, and Discinella schimperi (Navashin) Redhead specifically colonizes the mucilage producing cells of stems of Sphagnum squarrosum Crome. Eocronartium muscicola (Pers.) Fitzp. demonstrates a highly evolved host–parasite relationship in which the basidiocarp displaces the sporophyte and is fed directly by the gametophyte through specialized transfer tissues. Fungi such as Oidiodendron maius Barron are capable of decomposing moss cell walls that are generally resistant to decomposition because of their polyphenolic component. Mycorrhizal fungi, including Glomus, Suillus, and Endogone, have not been observed to form functional, nutrient-exchanging mycorrhizal interfaces with bryophytes, rather, they function as saprobes on moribund and senescent gametophytes. Finally, endophytic fungi may provide bryophyte hosts with greater tolerance to extreme pH or promote vegetative growth. In vivo observation of bryophyte–fungus interactions has provided insight into the types of interactions that occur; however to further understand the physiology, anatomy, and etiology of these interactions, it is necessary to culture bryophilous fungi in vitro and create artificial axenic systems for study.

scholarly journals Toxoplasma gondii co-opts the unfolded protein response to enhance migration and dissemination of infected host cells

2020 ◽  
Author(s):  
Leonardo Augusto ◽  
Jennifer Martynowicz ◽  
Parth H. Amin ◽  
Nada S. Alakhras ◽  
Mark H. Kaplan ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
The Body ◽  
Host Cells ◽  
Migratory Activity ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

AbstractToxoplasma gondii is an intracellular parasite that reconfigures its host cell to promote pathogenesis. One consequence of Toxoplasma parasitism is increased migratory activity of host cells, which facilitates dissemination. Here we show that Toxoplasma triggers the unfolded protein response (UPR) in host cells through calcium release from the endoplasmic reticulum (ER). We further found that host IRE1, an ER stress sensor protein activated during Toxoplasma infection, also plays a noncanonical role in actin remodeling by binding filamin A in infected cells. By inducing cytoskeletal remodeling via IRE1 oligomerization in host cells, Toxoplasma enhances host cell migration in vitro and dissemination of the parasite to host organs in vivo. Our study identifies novel mechanisms used by Toxoplasma to induce dissemination of infected cells, providing new insights into strategies for treatment of toxoplasmosis.ImportanceCells that are infected with the parasite Toxoplasma gondii exhibit heightened migratory activity, which facilitates dissemination of the infection throughout the body. In this study, we identify a new mechanism used by Toxoplasma to hijack its host cell and increase its mobility. We further show that the ability of Toxoplasma to increase host cell migration does not involve the enzymatic activity of IRE1, but rather IRE1 engagement with actin cytoskeletal remodeling. Depletion of IRE1 from infected host cells reduces their migration in vitro and significantly hinders dissemination of Toxoplasma in vivo. Our findings reveal a new mechanism underlying host-pathogen interactions, demonstrating how host cells are co-opted to spread a persistent infection around the body.

scholarly journals Toxoplasma gondii Co-opts the Unfolded Protein Response To Enhance Migration and Dissemination of Infected Host Cells

mBio ◽  
2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Leonardo Augusto ◽  
Jennifer Martynowicz ◽  
Parth H. Amin ◽  
Nada S. Alakhras ◽  
Mark H. Kaplan ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
The Body ◽  
Host Cells ◽  
Content Type ◽  
Migratory Activity ◽  
Unfolded Protein ◽  
The Unfolded Protein Response

ABSTRACT Toxoplasma gondii is an intracellular parasite that reconfigures its host cell to promote pathogenesis. One consequence of Toxoplasma parasitism is increased migratory activity of host cells, which facilitates dissemination. Here, we show that Toxoplasma triggers the unfolded protein response (UPR) in host cells through calcium release from the endoplasmic reticulum (ER). We further identify a novel role for the host ER stress sensor protein IRE1 in Toxoplasma pathogenesis. Upon infection, Toxoplasma activates IRE1, engaging its noncanonical role in actin remodeling through the binding of filamin A. By inducing cytoskeletal remodeling via IRE1 oligomerization in host cells, Toxoplasma enhances host cell migration in vitro and dissemination of the parasite to host organs in vivo. Our study has identified novel mechanisms used by Toxoplasma to induce dissemination of infected cells, providing new insights into strategies for treatment of toxoplasmosis. IMPORTANCE Cells that are infected with the parasite Toxoplasma gondii exhibit heightened migratory activity, which facilitates dissemination of the infection throughout the body. In this report, we identify a new mechanism used by Toxoplasma to hijack its host cell and increase its mobility. We further show that the ability of Toxoplasma to increase host cell migration involves not the enzymatic activity of IRE1 but rather IRE1 engagement with actin cytoskeletal remodeling. Depletion of IRE1 from infected host cells reduces their migration in vitro and significantly hinders dissemination of Toxoplasma in vivo. Our findings reveal a new mechanism underlying host-pathogen interactions, demonstrating how host cells are co-opted to spread a persistent infection around the body.

scholarly journals In Vitro Induction of Neospora caninum Bradyzoites in Vero Cells Reveals Differential Antigen Expression, Localization, and Host-Cell Recognition of Tachyzoites and Bradyzoites

2004 ◽  
Vol 72 (1) ◽  
pp. 576-583 ◽  
Author(s):  
Nathalie Vonlaufen ◽  
Nicole Guetg ◽  
Arunasalam Naguleswaran ◽  
Norbert Müller ◽  
Camilla Björkman ◽  
...  
Keyword(s):  
Host Cell ◽  
Cyst Wall ◽  
Neospora Caninum ◽  
Antigen Expression ◽  
Vero Cells ◽  
Dense Granule ◽  
Host Cells ◽  
Transmission Electron ◽  
Intracellular Parasites

ABSTRACT We report on an optimized method for the in vitro culture of tissue cyst-forming Neospora caninum bradyzoites in Vero cells and the separation of viable parasites from host cells. Treatment of tachyzoite-infected Vero cell cultures with 17 μM sodium nitroprusside for 8 days severely scaled down parasite proliferation, led to reduced expression of tachyzoite surface antigens, and induced the expression of the bradyzoite marker NcBAG1 and the cyst wall antigen recognized by the monoclonal antibody MAbCC2. Transmission electron microscopy demonstrated that intracellular parasites were located within parasitophorous vacuoles that were surrounded by a cyst wall-like structure, and the dense granule antigens NcGRA1, NcGRA2, and NcGRA7 were incorporated into the cyst wall. Adhesion-invasion assays employing purified tachyzoites and bradyzoites showed that tachyzoites adhered to, and invaded, Vero cells with higher efficiency than bradyzoites. However, removal of terminal sialic acid residues from either the host cell or the parasite surface increased the invasion of Vero cells by bradyzoites, but not tachyzoites.

ACIS, A Novel KepTide™, Binds to ACE-2 Receptor and Inhibits the Infection of SARS-CoV2 Virus in vitro in Primate Kidney Cells: Therapeutic Implications for COVID-19 (Preprint)

2020 ◽  
Author(s):  
Avik Sotira Scientific
Keyword(s):  
Social Life ◽  
Plaque Assay ◽  
Host Cells ◽  
Surface Glycoprotein ◽  
Crystallographic Structure ◽  
Therapeutic Implications ◽  
Biochemical Assays ◽  
Targeted Medicine

UNSTRUCTURED Coronavirus disease 2019 (COVID-19) is a severe acute respiratory syndrome (SARS) caused by a virus known as SARS-Coronavirus 2 (SARS-CoV2). Without a targeted-medicine, this disease has been causing a massive humanitarian crisis not only in terms of mortality, but also imposing a lasting damage to social life and economic progress of humankind. Therefore, an immediate therapeutic strategy needs to be intervened to mitigate this global crisis. Here, we report a novel KepTide™ (Knock-End Peptide) therapy that nullifies SARS-CoV2 infection. SARS-CoV2 employs its surface glycoprotein “spike” (S-glycoprotein) to interact with angiotensin converting enzyme-2 (ACE-2) receptor for its infection in host cells. Based on our in-silico-based homology modeling study validated with a recent X-ray crystallographic structure (PDB ID:6M0J), we have identified that a conserved motif of S-glycoprotein that intimately engages multiple hydrogen-bond (H-bond) interactions with ACE-2 enzyme. Accordingly, we designed a peptide, termed as ACIS (ACE-2 Inhibitory motif of Spike), that displayed significant affinity towards ACE-2 enzyme as confirmed by biochemical assays such as BLItz and fluorescence polarization assays. Interestingly, more than one biochemical modifications were adopted in ACIS in order to enhance the inhibitory action of ACIS and hence called as KEpTide™. Consequently, a monolayer invasion assay, plaque assay and dual immunofluorescence analysis further revealed that KEpTide™ efficiently mitigated the infection of SARS-CoV2 in vitro in VERO E6 cells. Finally, evaluating the relative abundance of ACIS in lungs and the potential side-effects in vivo in mice, our current study discovers a novel KepTide™ therapy that is safe, stable, and robust to attenuate the infection of SARS-CoV2 virus if administered intranasally. INTERNATIONAL REGISTERED REPORT RR2-https://doi.org/10.1101/2020.10.13.337584

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