RT Journal Article
T1 NcROP2 deletion reduces Neospora caninum virulence by altering parasite stage differentiation and hijacking host immune response
A1 Amieva, Rafael
A1 Coronado, Montserrat
A1 Powell, Jessica
A1 Arranz Solís, David
A1 Hassan, Musa A.
A1 Collantes Fernández, Esther
A1 Ortega Mora, Luis Miguel
A1 Horcajo Iglesias, María Del Pilar
AB IntroductionNeospora caninum is an apicomplexan parasite responsible for bovine neosporosis, a major cause of abortion in cattle worldwide. N. caninum rhoptry protein 2 (NcROP2) has been identified as an essential factor in host cell invasion and parasitophorous vacuole formation, making it a potential target for disease control strategies.MethodsIn this study, we generated NcRop2 knockout (NcΔROP2) mutants using CRISPR/Cas9 technology to assess their role in parasite virulence.ResultsIn a pregnant mouse model, NcΔROP2 parasites exhibited reduced virulence, as indicated by increased neonatal survival rates and lower parasite burden in the brain and attenuated clinical signs in the dams compared to the wild-type (Nc-Spain7) parental strain. Additionally, the NcΔROP2 mutants exhibited impaired proliferation and significantly induced the expression of interferon-stimulated genes in bovine monocyte-derived macrophages infected in vitro for 60 hours. Transcriptomic analysis further revealed a shift in parasite gene expression, with an upregulation of stress-related and bradyzoite markers. Functional assays confirmed that NcΔROP2 parasites were less susceptible to IFN-γ-mediated inhibition and displayed an enhanced ability to convert to the semi-dormant bradyzoite stage.DiscussionThese findings highlight NcROP2 as a key virulence factor involved in immune evasion and parasite proliferation, providing new insights into N. caninum infection pathogenesis and potential avenues for vaccine development.
PB Frontiers Media
YR 2025
FD 2025
LK https://hdl.handle.net/20.500.14352/124760
UL https://hdl.handle.net/20.500.14352/124760
LA eng
NO Amieva, R., Coronado, M., Powell, J., Arranz-Solís, D., Hassan, M. A., Collantes-Fernández, E., Ortega-Mora, L. M., & Horcajo, P. (2025). NcROP2 deletion reduces Neospora caninum virulence by altering parasite stage differentiation and hijacking host immune response. Frontiers in immunology, 16, 1617570. https://doi.org/10.3389/fimmu.2025.1617570
NO Author contributions: RA: Methodology, Validation, Investigation, Visualization, Writing – original draft, Formal analysis. MC: Formal analysis, Methodology, Writing – review & editing. JP: Writing – review & editing, Methodology. DA: Methodology, Writing – review & editing. MH: Supervision, Writing – review & editing. EC: Resources, Funding acquisition, Visualization, Project administration, Writing – review & editing, Supervision. LO: Visualization, Resources, Project administration, Writing – review & editing, Funding acquisition, Supervision. PH: Visualization, Supervision, Funding acquisition, Resources, Project administration, Writing – review & editing.{Citation}
NO Ministerio de Ciencia, Innovación y Universidades ( España)
NO Comunidad de Madrid
DS Docta Complutense
RD 8 abr 2026