Immunological characterization of<i>Neospora caninum</i>cyclophilin

Kameyama, Kyohko; Nishimura, Maki; Myagmarsuren, Punsantsogvoo; Ibrahim, Hany M.; Xuan, Xuenan; Furuoka, Hidefumi; Nishikawa, Yoshifumi

doi:10.1017/s0031182011002022

Cited by 13 publications

(11 citation statements)

References 30 publications

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“…S1A to C and 2A in the supplemental material). NcCYPdeficient parasites were also generated because it has been suggested that NcCYP induces IFN-␥ production by peripheral blood mononuclear cells (24) and triggers the migration of murine and bovine cells (18) (Fig. 2B; see also Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Similarly, the Toxoplasma rhoptry proteins, ROP5, ROP16, ROP18, and ROP38, contain protein kinase domains (14) and subvert and coopt host-cell functions (15)(16)(17). Among other molecules of N. caninum, cyclophilin (NcCYP) appears to contribute to host cell migration (18) and profilin (NcPF) induces strong IFN-␥ and interleukin-12 (IL-12) responses (19). Therefore, the effector proteins exported by N. caninum are key players in neosporosis.…”

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confidence: 99%

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Neospora caninum Dense Granule Protein 7 Regulates the Pathogenesis of Neosporosis by Modulating Host Immune Response

Nishikawa

Shimoda

Fereig

et al. 2018

Appl Environ Microbiol

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is a protozoan parasite closely related to Neosporosis caused by is considered one of the main causes of abortion in cattle and nervous-system dysfunction in dogs, and identification of the virulence factors of this parasite is important for the development of control measures. Here, we used a luciferase reporter assay to screen the dense granule proteins genes of , and we found that NcGRA6, NcGRA7, and NcGRA14 are involved in the activation of the NF-κB, calcium/calcineurin, and cAMP/PKA signals. To analyze the functions of these proteins and cyclophilin, we successfully knocked out their genes in the Nc1 strain using plasmids containing the CRISPR/Cas9 components. Among the deficient lines, the -deficient parasites showed reduced virulence in mice. An RNA sequencing analysis of infected macrophage cultures showed that NcGRA7 mainly regulates the host cytokine and chemokine production. The levels of gamma interferon in the ascites fluid, CXCL10 expression in the peritoneal cells, and CCL2 expression in the spleen were lower 5 days after infection with the-deficient parasite than after infection with the parental strain. The parasite burden and the degree of necrosis in the brains of mice infected with the -deficient parasite were also lower than in those of the parental strain. Collectively, our data suggest that both the NcGRA7-dependent activation of the inflammatory response and the parasite burden are important in virulence. invades and replicates in a broad range of host species and cells within those hosts. The effector proteins exported by induce its pathogenesis by modulating the host immunity. We show that most of the transcriptomic effects in-infected cells depend upon the activity of NcGRA7. A deficiency in NcGRA7 reduced the virulence of the parasite in mice. This study demonstrates the importance of NcGRA7 in the pathogenesis of neosporosis.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Neospora caninum Dense Granule Protein 7 Regulates the Pathogenesis of Neosporosis by Modulating Host Immune Response

Nishikawa

Shimoda

Fereig

et al. 2018

Appl Environ Microbiol

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“…The CCR5 chemokine receptor is also a key player in the immune response against N. caninum , because mice deficient in the CCR5 gene are susceptible to the infection [ 1 ]. Additionally, the interaction of CCR5 with parasite-derived cyclophilin triggers migration and activation of innate cells [ 17 , 24 ]. Thus, MyD88- or TRIF-dependent pathways through TLRs or chemokine receptors can stimulate host immune responses against infection with N. caninum .…”

Section: Host-immune Responses Against N Caninum mentioning

confidence: 99%

Towards a preventive strategy for neosporosis: challenges and future perspectives for vaccine development against infection with <i>Neospora caninum</i>

Nishikawa

2017

The Journal of Veterinary Medical Science

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Neosporosis is caused by the intracellular protozoan parasite Neospora caninum. This major disease-causing pathogen is responsible for inducing abortion in cattle, and these adverse events occur sporadically all over the world, including Japan. Currently, there are no vaccines on the market against infection with N. caninum. Because live and attenuated vaccines against N. caninum have had safety and effectiveness issues, development of a next-generation vaccine is urgently required. To develop a vaccine against neosporosis, my laboratory has been focused on the following: 1) understanding the host immune responses against Neospora infection, 2) identifying vaccine antigens and 3) developing an effective antigen-delivery system. The research strategy taken in my laboratory will have strong potential to progress current understanding of the pathogenesis of N. caninum infection and promote development of a novel subunit vaccine based on the specific vaccine antigen with an antigen-delivery system for controlling neosporosis.

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“…In the case of N. caninum , excreted and secreted antigens triggered monocytic cell migration to the site of infection in a CCR5-dependent manner [ 12 ]. Moreover, N. caninum cyclophilin caused CCR5-dependent migration of murine and bovine cells [ 13 ]. Thus, CCR5 regulates the type of immune cell migration and cytokine production required for host control of parasites in T. gondii and N. caninum infections.…”

Section: Introductionmentioning

confidence: 99%

Role of the chemokine receptor CCR5-dependent host defense system in Neospora caninum infections

et al. 2015

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BackgroundNeospora caninum, a Toxoplasma gondii-like obligate intracellular parasite, causes abortion in cattle and neurological signs in canines. To understand neosporosis better, studies on host cell migration and host immune responses during the early phase of infection are important. Although the C-C chemokine receptor 5 (CCR5) plays a crucial role in immune cell migration, the role played by it in protective immunity against N. caninum is poorly understood.MethodsCCR5−/− mice were used to investigate their sensitivity levels to N. caninum infection and their ability to activate immune cells against this parasite.ResultsIncreased mortality and neurological impairment were observed in the N. caninum-infected CCR5−/− mice. In comparison with wild-type mice, CCR5−/− mice experienced poor migration of dendritic cells and natural killer T cells to the site of infection. Dendritic cells in an in vitro culture from CCR5−/− mice could not be activated upon infection with N. caninum. Furthermore, higher levels of IFN-γ and CCL5 expression, which are associated with brain tissue damage, were observed in the brain tissue of CCR5−/− mice during the acute phase of the infection, while there was no significant difference in the parasite load between the wild-type and CCR5−/− animals. Additionally, a primary microglia culture from CCR5−/− mice showed lower levels of IL-6 and IL-12 production against N. caninum parasites.ConclusionsOur findings show that migration and activation of immune cells via CCR5 is required for controlling N. caninum parasites during the early phase of the infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-014-0620-5) contains supplementary material, which is available to authorized users.

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Immunological characterization ofNeospora caninumcyclophilin

Cited by 13 publications

References 30 publications

Neospora caninum Dense Granule Protein 7 Regulates the Pathogenesis of Neosporosis by Modulating Host Immune Response

Neospora caninum Dense Granule Protein 7 Regulates the Pathogenesis of Neosporosis by Modulating Host Immune Response

Towards a preventive strategy for neosporosis: challenges and future perspectives for vaccine development against infection with <i>Neospora caninum</i>

Role of the chemokine receptor CCR5-dependent host defense system in Neospora caninum infections

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