scholarly journals Toll-Like Receptor 3–TRIF Pathway Activation by Neospora caninum RNA Enhances Infection Control in 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 ◽  
...  
Keyword(s):  
Neospora Caninum ◽  
Parasitophorous Vacuole ◽  
Protozoan Parasite ◽  
Interferon Response ◽  
Economic Losses ◽  
Toll Like Receptor ◽  
Content Type ◽  
Pathway Activation ◽  
Th1 Immune Responses

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.

scholarly journals TLR3-TRIF pathway activation by Neospora caninum RNA enhances infection control

2018 ◽  
Author(s):  
Vanessa dos Santos Miranda ◽  
Flávia Batista Ferreira França ◽  
Mylla Spirandelli da Costa ◽  
Vanessa Resende Souza Silva ◽  
Caroline Martins Mota ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neospora Caninum ◽  
Parasitophorous Vacuole ◽  
Parasite Burden ◽  
Protozoan Parasite ◽  
Economic Losses ◽  
Pathway Activation ◽  
Ifn Γ ◽  
Th1 Immune Responses

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.

scholarly journals From Signaling Pathways to Distinct Immune Responses: Key Factors for Establishing or Combating Neospora caninum Infection in Different Susceptible Hosts

Pathogens ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 384 ◽  
Author(s):  
Ragab M. Fereig ◽  
Yoshifumi Nishikawa
Keyword(s):  
Host Cell ◽  
Neospora Caninum ◽  
Protozoan Parasite ◽  
Survey Method ◽  
Economic Losses ◽  
Key Factors ◽  
Caninum Infection ◽  
Successful Infection ◽  
Comprehensive Survey

Neospora caninum is an intracellular protozoan parasite affecting numerous animal species. It induces significant economic losses because of abortion and neonatal abnormalities in cattle. In case of infection, the parasite secretes numerous arsenals to establish a successful infection in the host cell. In the same context but for a different purpose, the host resorts to different strategies to eliminate the invading parasite. During this battle, numerous key factors from both parasite and host sides are produced and interact for the maintaining and vanishing of the infection, respectively. Although several reviews have highlighted the role of different compartments of the immune system against N. caninum infection, each one of them has mostly targeted specific points related to the immune component and animal host. Thus, in the current review, we will focus on effector molecules derived from the host cell or the parasite using a comprehensive survey method from previous reports. According to our knowledge, this is the first review that highlights and discusses immune response at the host cell–parasite molecular interface against N. caninum infection in different susceptible hosts.

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
Keyword(s):  
Neospora Caninum ◽  
Parasitophorous Vacuole ◽  
Protozoan Parasite ◽  
Current Data ◽  
Intracellular Killing ◽  
Apicomplexan Parasites ◽  
Obligate Intracellular ◽  
Animal Pathogens ◽  
Intracellular Protozoan Parasite

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.

scholarly journals Initial phospholipid-dependent Irgb6 targeting to Toxoplasma gondii vacuoles mediates host defense

2019 ◽  
Vol 3 (1) ◽  
pp. e201900549 ◽  
Author(s):  
Youngae Lee ◽  
Hiroshi Yamada ◽  
Ariel Pradipta ◽  
Ji Su Ma ◽  
Masaaki Okamoto ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Parasitophorous Vacuole ◽  
Protozoan Parasite ◽  
Host Cells ◽  
Interferon Response ◽  
Obligate Intracellular ◽  
Membrane Bound ◽  
Ifn Γ ◽  
Intracellular Protozoan Parasite

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.

scholarly journals Evaluation of a competitive inhibition ELISA based on the recombinant protein tSAG1 to detect anti–Neospora caninum antibodies in cattle

2020 ◽  
Vol 32 (3) ◽  
pp. 401-408
Author(s):  
María B. Novoa ◽  
Beatriz S. Valentini ◽  
Macarena Sarli ◽  
Susana M. Torioni-de-Echaide ◽  
María E. Primo ◽  
...  
Keyword(s):  
Large Scale ◽  
Competitive Inhibition ◽  
Neospora Caninum ◽  
Management Strategies ◽  
Protozoan Parasite ◽  
Economic Losses ◽  
Serum Samples ◽  
Beef Cow ◽  
Inhibition Elisa ◽  
Scale Detection

Neospora caninum is a protozoan parasite that causes abortion and important economic losses in cattle worldwide. There are no treatments or vaccines available; disease control is based on diagnosis and herd management strategies. We developed, validated, and evaluated under field conditions a competitive inhibition ELISA based on the truncated SAG1 protein (tSAG1), expressed in Escherichia coli, and the RafNeo5 monoclonal antibody (ciELISAtSAG1). A criterion based on the 3-y sequential serologic analysis of 230 dairy cows by IFAT was used as the gold standard. The assay was validated using 860 serum samples from cows that were consistently positive or negative by IFAT throughout the study period. ciELISAtSAG1 was then used to evaluate the prevalence of neosporosis in 16 beef cow herds (22 samples per herd, 352 total samples). The results were compared with those from IFAT and a commercial cELISA (cELISAVMRD). The ciELISAtSAG1 cutoff was ≥ 29%I, with a diagnostic sensitivity of 98.7% (95% CI = 96.8–99.7%) and a diagnostic specificity of 97.9% (95% CI = 96.4–99.0%). Concordance among IFAT, cELISAVMRD, and ciELISAtSAG1 was 90.3%. The agreement (κ) between ciELISAtSAG1 and the other 2 tests was ≥ 0.81. The overall prevalence of neosporosis in the 16 beef herds was 30% (range: 5–60%). The ciELISAtSAG1 could be useful for large-scale detection of anti– N. caninum antibodies in cattle and seroepidemiologic investigations, given its appropriate sensitivity and specificity, and the simplicity of production.

Investigating the role of wild carnivores in the epidemiology of bovine neosporosis

Parasitology ◽  
2012 ◽  
Vol 140 (3) ◽  
pp. 296-302 ◽  
Author(s):  
PETER STUART ◽  
ANNETTA ZINTL ◽  
THEO DE WAAL ◽  
GRACE MULCAHY ◽  
CONALL HAWKINS ◽  
...  
Keyword(s):  
Neospora Caninum ◽  
American Mink ◽  
Protozoan Parasite ◽  
Meles Meles ◽  
Pcr Analysis ◽  
Red Foxes ◽  
Bovine Neosporosis ◽  
Low Prevalence ◽  
Local Ecology

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.

Endogenous and exogenous transplacental transmission of Neospora caninum – how the route of transmission impacts on epidemiology and control of disease

Parasitology ◽  
2009 ◽  
Vol 136 (14) ◽  
pp. 1895-1900 ◽  
Author(s):  
D. J. L. WILLIAMS ◽  
C. S. HARTLEY ◽  
C. BJÖRKMAN ◽  
A. J. TREES
Keyword(s):  
Immune Response ◽  
Vertical Transmission ◽  
Neospora Caninum ◽  
Protozoan Parasite ◽  
Transplacental Transmission ◽  
Highly Efficient ◽  
Route Of Transmission ◽  
And Control

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.

scholarly journals Role of Toll Interleukin-1 Receptor (IL-1R) 8, a Negative Regulator of IL-1R/Toll-Like Receptor Signaling, in Resistance to Acute Pseudomonas aeruginosa Lung Infection

2011 ◽  
Vol 80 (1) ◽  
pp. 100-109 ◽  
Author(s):  
Tania Véliz Rodriguez ◽  
Federica Moalli ◽  
Nadia Polentarutti ◽  
Moira Paroni ◽  
Eduardo Bonavita ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Interleukin 1 ◽  
Bacterial Load ◽  
Lung Infection ◽  
Negative Regulator ◽  
Current Evidence ◽  
Toll Like Receptor ◽  
Content Type ◽  
Deficient Mice

ABSTRACTToll interleukin-1 receptor (IL-1R) 8 (TIR8), also known as single Ig IL-1 receptor (IL-R)-related molecule, or SIGIRR, is a member of the IL-1R-like family, primarily expressed by epithelial cells. Current evidence suggests that TIR8 plays a nonredundant role as a negative regulatorin vivounder different inflammatory conditions that are dependent on IL-R and Toll-like receptor (TLR) activation. In the present study, we examined the role of TIR8 in innate resistance to acute lung infections caused byPseudomonas aeruginosa, a Gram-negative pathogen responsible for life-threatening infections in immunocompromised individuals and cystic fibrosis patients. We show that Tir8 deficiency in mice was associated with increased susceptibility to acuteP. aeruginosainfection, in terms of mortality and bacterial load, and to exacerbated local and systemic production of proinflammatory cytokines (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], IL-1β, and IL-6) and chemokines (CXCL1, CXCL2, and CCL2). It has been reported that host defense againstP. aeruginosaacute lung infection can be improved by blocking IL-1 since exaggerated IL-1β production may be harmful for the host in this infection. In agreement with these data, IL-1RI deficiency rescues the phenotype observed in Tir8-deficient mice: in Tir8−/−IL-1RI−/−double knockout mice we observed higher survival rates, enhanced bacterial clearance, and reduced levels of local and systemic cytokine and chemokine levels than in Tir8-deficient mice. These results suggest that TIR8 has a nonredundant effect in modulating the inflammation caused byP. aeruginosa, in particular, by negatively regulating IL-1RI signaling, which plays a major role in the pathogenesis of this infectious disease.

scholarly journals Epidemiology and Control of Neosporosis and Neospora caninum

2007 ◽  
Vol 20 (2) ◽  
pp. 323-367 ◽  
Author(s):  
J. P. Dubey ◽  
G. Schares ◽  
L. M. Ortega-Mora
Keyword(s):  
Life Cycle ◽  
New Genus ◽  
Neospora Caninum ◽  
Protozoan Parasite ◽  
Zoonotic Potential ◽  
Human Tissues ◽  
New Genus And Species ◽  
Serious Disease ◽  
And Control

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.

scholarly journals Biotinylation of the Neospora caninum parasitophorous vacuole reveals novel dense granule proteins

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Congshan Yang ◽  
Chenrong Wang ◽  
Jing Liu ◽  
Qun Liu
Keyword(s):  
Neospora Caninum ◽  
Gene Knockout ◽  
Parasitophorous Vacuole ◽  
Dense Granule ◽  
Host Cells ◽  
Spectrometric Analysis ◽  
Data Set ◽  
Dense Granules ◽  
Granule Proteins

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

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