scholarly journals ToxoplasmaRhoptries: Unique Secretory Organelles and Source of Promising Vaccine Proteins for Immunoprevention of Toxoplasmosis

2008 ◽  
Vol 2008 ◽  
pp. 1-7 ◽  
Author(s):  
Henryka Dlugonska

Toxoplasma gondiiis an obligate intracellular protozoan parasite classified in the phylum Apicomplexa, which includes numerous notable human and animal pathogens (Plasmodiumspecies,Cryptosporidiumspecies,Neospora caninum, etc.). The invasive stages of apicomplexans are characterized by the presence of an apical complex composed of specialized cytoskeletal and secretory organelles, including rhoptries. Rhoptries, unique apical secretory organelles shared exclusively by all apicomplexan parasites, are known to be involved in an active parasite's penetration into the host cell associated with the biogenesis of specific intracellular compartment, parasitophorous vacuole in which the parasite multiplies intensively, avoiding intracellular killing. Due to the key biological role of rhoptries, rhoptry proteins have recently become vaccine candidates for the prevention of several parasitoses, toxoplasmosis among them. The article presents current data onT. gondiirhoptries biology and new approaches to the development of effective vaccines against toxoplasmosis using rhoptry antigens.

2019 ◽  
Vol 3 (1) ◽  
pp. e201900549 ◽  
Author(s):  
Youngae Lee ◽  
Hiroshi Yamada ◽  
Ariel Pradipta ◽  
Ji Su Ma ◽  
Masaaki Okamoto ◽  
...  

Toxoplasma gondii is an obligate intracellular protozoan parasite capable of infecting warm-blooded animals by ingestion. The organism enters host cells and resides in the cytoplasm in a membrane-bound parasitophorous vacuole (PV). Inducing an interferon response enables IFN-γ–inducible immunity-related GTPase (IRG protein) to accumulate on the PV and to restrict parasite growth. However, little is known about the mechanisms by which IRG proteins recognize and destroy T. gondii PV. We characterized the role of IRG protein Irgb6 in the cell-autonomous response against T. gondii, which involves vacuole ubiquitination and breakdown. We show that Irgb6 is capable of binding a specific phospholipid on the PV membrane. Furthermore, the absence of Irgb6 causes reduced targeting of other effector IRG proteins to the PV. This suggests that Irgb6 has a role as a pioneer in the process by which multiple IRG proteins access the PV. Irgb6-deficient mice are highly susceptible to infection by a strain of T. gondii avirulent in wild-type mice.


2019 ◽  
Vol 87 (4) ◽  
Author(s):  
Vanessa dos Santos Miranda ◽  
Flávia Batista Ferreira França ◽  
Mylla Spirandelli da Costa ◽  
Vanessa Resende Souza Silva ◽  
Caroline Martins Mota ◽  
...  

ABSTRACT Neospora caninum is a protozoan parasite closely related to Toxoplasma gondii and has been studied for causing neuromuscular disease in dogs and abortions in cattle. It is recognized as one of the main transmissible causes of reproductive failure in cattle and consequent economic losses to the sector. In that sense, this study aimed to evaluate the role of Toll-like receptor 3 (TLR3)–TRIF-dependent resistance against N. caninum infection in mice. We observed that TLR3−/− and TRIF−/− mice presented higher parasite burdens, increased inflammatory lesions, and reduced production of interleukin 12p40 (IL-12p40), tumor necrosis factor (TNF), gamma interferon (IFN-γ), and nitric oxide (NO). Unlike those of T. gondii, N. caninum tachyzoites and RNA recruited TLR3 to the parasitophorous vacuole (PV) and translocated interferon response factor 3 (IRF3) to the nucleus. We also observed that N. caninum upregulated the expression of TRIF in murine macrophages, which in turn upregulated IFN-α and IFN-β in the presence of the parasite. Furthermore, TRIF−/− infected macrophages produced lower levels of IL-12p40, while exogenous IFN-α replacement was able to completely restore the production of this key cytokine. Our results show that the TLR3-TRIF signaling pathway enhances resistance against N. caninum infection in mice, since it improves Th1 immune responses that result in controlled parasitism and reduced tissue inflammation, which are hallmarks of the disease.


2018 ◽  
Author(s):  
Vanessa dos Santos Miranda ◽  
Flávia Batista Ferreira França ◽  
Mylla Spirandelli da Costa ◽  
Vanessa Resende Souza Silva ◽  
Caroline Martins Mota ◽  
...  

AbstractNeospora caninum is a protozoan parasite closely related to Toxoplasma gondii and has been studied for causing neuromuscular disease in dogs and abortions in cattle. It is recognized as the major cause of economic losses in bovine products. In that sense, this study aimed to evaluate the role of TLR3-TRIF dependent resistance against N. caninum infection. We observed that TLR3−/− and TRIF−/− mice presented higher parasite burden, increased inflammatory lesions and reduced production of IL-12p40, TNF, IFN-γ, and NO. Differently from T. gondii, N. caninum tachyzoites and its RNA recruited TLR3 and IRF3 to the parasitophorous vacuole (PV). We observed that N. caninum upregulated the expression of TRIF in macrophages, which by its turn upregulated IFN-α and IFN-β in the presence of the parasite. Furthermore, TRIF−/− infected macrophages produced lower levels of IL-12p40 and IFN-α replacement was able to completely restore the production of this key cytokine. Our results have shown that TLR3-TRIF signaling pathway enhances resistance against N. caninum infection, since it improves Th1 immune responses that control parasitism and tissue inflammation, which are hallmarks of the disease.


2006 ◽  
Vol 60 (3-4) ◽  
pp. 223-231
Author(s):  
Tamara Ilic ◽  
Sanda Dimitrijevic

Neospora caninum is an obligate intracellular protozoan parasite which primarily causes diseases in dogs and cattle all over the world. It was first described in Norway in the mid-eighties in dogs, after which, until the present time, clinical neosporosis was proven in sheep, goats, deer, rhinoceroses, horses, and experimental rodents. Antibodies against N. caninum have been found also in the serum of water buffalo, red and gray foxes, coyotes, camels, and felines. Due to the similarity of this Coccidia with Toxoplasma gondi, the neosporosis was for a series of years incorrectly diagnozed as toxoplasmosis. Domestic canines, dogs, are the only real host for N. caninum. Its life cycle covers three stages of development: tachyzoites, tissue cysts and oocysts. Carnivores are infected by ingesting parts of infected tissue which contain tissue cysts with bradyzoites. The dominant pathway of transmission of this cause in cattle is transplacentary infection, but cattle can also be infected by ingestion of feed or water contaminated by sporulated oo-cysts of N. caninum. Bitches can be subclinical carriers of the parasite, when they pass on the cause transplacentarily, which results in more than one litter being born with the infection. Neosporosis today appears as the main cause of abortions and neonatal deaths in dairy cows and fattening cattle in almost all parts of the world, but with the highest incidence in the United States (US), New Zealand, The Netherlands, and Germany. The treatment of this disease has not been fully determined, but medicines used for the treatment of toxoplasmosis have yielded certain good results. There is no verified vaccine that would prevent undesired abortions in cattle. .


Parasitology ◽  
2012 ◽  
Vol 140 (3) ◽  
pp. 296-302 ◽  
Author(s):  
PETER STUART ◽  
ANNETTA ZINTL ◽  
THEO DE WAAL ◽  
GRACE MULCAHY ◽  
CONALL HAWKINS ◽  
...  

SUMMARYNeospora caninumis a protozoan parasite, primarily associated with bovine abortion. The only definitive hosts discovered to date are carnivores. This study aimed to identify the role of mammalian carnivores in the epidemiology of bovine neosporosis. A sample bank of serum, fecal and brain samples was established: American mink (Mustela vison), red foxes (Vulpes vulpes), pine martens (Martes martes), badgers (Meles meles), stoats (Mustela erminea), otters (Lutra lutra) and feral ferrets (Mustela putorius). Approximately 1% of mink and 1% of fox samples were positive by IFAT. According to PCR analysis of DNA extracted from brain tissue, 3% of the mink, 4% of the otters and 6% of the foxes examined were infected withN. caninum.All fecal samples tested negative forN. caninumDNA (n = 311), suggesting that the species that tested positive were intermediate not definitive hosts. This is the first time that tissues from mustelids have tested positive forN. caninum. The need to test 2 relatively large (∼200 mg) targeted parts of the brain to avoid false negatives was also identified. The relatively low prevalence ofN. caninumin Irish carnivores suggests that the local ecology of a species has an important influence on its epidemiological role.


Parasitology ◽  
2009 ◽  
Vol 136 (14) ◽  
pp. 1895-1900 ◽  
Author(s):  
D. J. L. WILLIAMS ◽  
C. S. HARTLEY ◽  
C. BJÖRKMAN ◽  
A. J. TREES

SUMMARYVertical transmission of the protozoan parasite, Neospora caninum is highly efficient and can take two forms – endogenous transplacental transmission resulting from activation of the quiescent bradyzoite stage during pregnancy or exogenous transplacental transmission resulting from ingestion of oocysts during pregnancy. Calves born carrying infection derived from either endogenous or exogenous transplacental transmission are capable of infecting their offspring when they start to breed. This review considers firstly the frequency with which exogenous and endogenous transmission occur, secondly the role of the immune response in controlling N. caninum infection and thirdly how the parasite persists in an immune-competent host and is re-activated during pregnancy.


2007 ◽  
Vol 20 (2) ◽  
pp. 323-367 ◽  
Author(s):  
J. P. Dubey ◽  
G. Schares ◽  
L. M. Ortega-Mora

SUMMARY Neospora caninum is a protozoan parasite of animals. Until 1988, it was misidentified as Toxoplasma gondii. Since its first recognition in dogs in 1984 and the description of the new genus and species Neospora caninum in 1988, neosporosis has emerged as a serious disease of cattle and dogs worldwide. Abortions and neonatal mortality are a major problem in livestock operations, and neosporosis is a major cause of abortion in cattle. Although antibodies to N. caninum have been reported, the parasite has not been detected in human tissues. Thus, the zoonotic potential is uncertain. This review is focused mainly on the epidemiology and control of neosporosis in cattle, but worldwide seroprevalences of N. caninum in animals and humans are tabulated. The role of wildlife in the life cycle of N. caninum and strategies for the control of neosporosis in cattle are discussed.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Congshan Yang ◽  
Chenrong Wang ◽  
Jing Liu ◽  
Qun Liu

Abstract Background Neospora caninum is an obligate intracellular parasite that invades host cells and replicates within the parasitophorous vacuole (PV), which resists fusion with host cell lysosomal compartments. To modify the PV, the parasite secretes an array of proteins, including dense granule proteins (GRAs). The vital role of GRAs in the Neospora life cycle cannot be overestimated. Despite this important role, only a subset of these proteins have been identified, and most of their functions have not been elucidated. Our previous study demonstrated that NcGRA17 is specifically targeted to the delimiting membrane of the parasitophorous vacuole membrane (PVM). In this study, we utilize proximity-dependent biotin identification (BioID) to identify novel components of the dense granules. Methods NcGRA17 was BirA* epitope-tagged in the Nc1 strain utilizing the CRISPR/Cas9 system to create a fusion of NcGRA17 with the biotin ligase BirA*. The biotinylated proteins were affinity-purified for mass spectrometric analysis, and the candidate GRA proteins from BioID data set were identified by gene tagging. To verify the biological role of novel identified GRA proteins, we constructed the NcGRA23 and NcGRA11 (a–e) knockout strains using the CRISPR/Cas9 system and analyzed the phenotypes of these mutants. Results Using NcGRA17-BirA* fusion protein as bait, we have identified some known GRAs and verified localization of 11 novel GRA proteins by gene endogenous tagging or overexpression in the Nc1 strain. We proceeded to functionally characterize NcGRA23 and NcGRA11 (a–e) by gene knockout. The lack of NcGRA23 or NcGRA11 (a–e) did not affect the parasite propagation in vitro and virulence in vivo. Conclusions In summary, our findings reveal that BioID is effective in discovering novel constituents of N. caninum dense granules. The exact biological functions of the novel GRA proteins are yet unknown, but this could be explored in future studies. Graphical abstract


2020 ◽  
Vol 71 (1) ◽  
pp. 2018
Author(s):  
S. KASAP ◽  
S. ERTUNC ◽  
E. M. TEMIZEL ◽  
S. SENTURK

Neospora caninum is a intracellular protozoan parasite and is one of the major causes of repeated abortions, foetal malformations, pre-term deliveries, stillbirth and possible loss of milk yield in livestock. The presence of specific antibodies against N. caninum in the blood serum of dairy cows is investigated in the present study. A total of 184 blood serum samples of dairy cows were examined in Bursa province in the Marmara Region. N. caninum antibodies were measured using an indirect enzyme-linked immunosorbent assay (ELISA) (The Svanovir Neospora-Ab ELISA). From the total sample, antibodies to N. caninum were detected in 62 of the 184 examined cows (33.3%) and neurological findings were seen in a calf.


2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Mitra Salehi ◽  
Hosein Nezami ◽  
Hamid Reza Niazkar

Toxoplasma gondii is a zoonotic obligate intracellular protozoan parasite that infects warm-blooded animals as well as humans worldwide. The purpose of this study was to delineate the prevalence of Toxoplasma infection in aborted fetuses of sheep in North Khorasan province, Iran. Three hundred and ninety-nine samples of the liver (133 samples), placenta (133 samples), and brain (133 samples) from 133 aborted fetuses of sheep were collected from 2015 to 2017. The ages of aborted fetuses were higher than 120 days’ gestational age in this study. According to the samples, sixteen out of 133 aborted fetuses of sheep were infected with T. gondii. Toxoplasma DNA was found in the placenta (68.75%) and liver (31.25%) samples of infected fetuses using the PCR method. The highest and lowest rates of Toxoplasma infection were observed during 2016 and 2017, respectively. Shirvan and Faruj provinces were recognized as the two most infected districts among others. There was a significant difference between the year and abortion rate in sheep due to infection by the Toxoplasma parasite (P<0.05). Furthermore, no significant difference between the prevalence of T. gondii infection and aborted fetuses was seen (P>0.05) in different areas. According to the present study, T. gondii infection can be one of the causes of fetus abortion of sheep in North Khorasan province, Iran.


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