Establishment of a model of Neospora caninum infection in pregnant mice

Jia, Lijun; Xie, Suzhu; Li, Jixu; Li, Hang; Wang, Hao; Zhao, Shaowei; Zhang, Shuang

doi:10.1007/s00436-020-06903-0

Cited by 7 publications

(4 citation statements)

References 23 publications

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“…1d). In accordance, a recent study by Jia et al (2020) showed that IFN−γ and IL-4 secreted by placental cells obtained from N. caninum infected mice were signi cantly higher compare to those from control mice. A recent study by Giménez-Pelayo et al ( 2019), suggest that pro-in ammatory cytokines could have a minor impact in placental damage by N. caninum than postulated previously, but other mechanisms should be implicated in the injury of the placenta in vivo.…”

Section: Resultssupporting

confidence: 87%

Dysfunction, oxidative stress markers, and cytokine expression in the placentae of mice experimentally infected with Neospora caninum

Morales,

Lagorio,

Corigliano

et al. 2023

Parasitol Res

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Neosporosis is the major cause of abortion and reproductive failures in cattle, leading to important economic losses. In this study, we evaluated the impact of Neospora caninum infection on oxidative stress (OS) markers and local cytokine mRNA expression at the placenta, as well as its effect on the progesterone (P 4 ) serum levels and systemic cytokine pro le in a pregnant mouse model. Infected pregnant mice (NC-1 group) showed increased percentages of foetal losses and IFN-γ serum levels, decreased serum progesterone, increased mRNA expression levels of both Th1 (IFN-γ and TNF-α) and Th2 (IL-4) cytokines and inhibited expression of TGF-β1 (Treg) compare to control dams (CONTROL group). In addition, lipid peroxidation and ROS were increased, whereas the antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT) showed impairment in their activities in the placentae from infected mice compared to control mice. These ndings demonstrate that multiple factors, including OS, are involved in foetal losses associated with N. caninum infection in mice, thus OS contribution to the placental physiopathology of neosporosis in other hosts must not be ruled out.

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Section: Resultssupporting

confidence: 87%

Dysfunction, oxidative stress markers, and cytokine expression in the placentae of mice experimentally infected with Neospora caninum

Morales,

Lagorio,

Corigliano

et al. 2023

Parasitol Res

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“…The presence of the vaginal mucoid plug determined the start of the gestational period after females matting for one night and 1 day (day 59). All pregnant dams except the negative control group were challenged subcutaneously with 2 × 10 5 NC-1 tachyzoites on day 7 of gestation (day 66) according to the best gestation period of vertical transmission previously reported (López-Pérez et al 2006 ; Jia et al 2020 ). The productive infection in mice was confirmed using blood samples without EDTA collected 1 day after the protozoan inoculation (day 67), and we extracted the DNA and ran the PCR according to the method explained below.…”

Section: Methodsmentioning

confidence: 99%

“…The peptides based on immunogenic fractions of native antigens could improve their immunogenicity, adding new knowledge to developing new-generation vaccines against neosporosis. That could be assayed in mice which are a valid model for vaccine candidate research (Aguado-Martínez et al 2017 ) due to BALB/c mice developing a productive infection with cerebral lesions (Lindsay et al 1995 ; Jia et al 2020 ) and vertical transmission to newborn pups after infection with N. caninum (Tang et al 2023 ). This study evaluated in BALB/c mice potential vaccines composed of recombinant peptides rsNcGRA1 and rsNcSAG4, designed by predicting T and B epitopes of NcSAG4 and NcGRA1 antigens and produced in the yeast system of Komagataella phaffii concerning the immunogenicity and protection against neosporosis, demonstrating that combined peptides and rsNcGRA1 alone at standard doses can induce a proper immune response that controls the chronic infection in dams and reduces vertical transmission in pups.…”

Section: Introductionmentioning

confidence: 99%

Immunisation with Neospora caninum subunits rsNcSAG4 and rsNcGRA1 (NcSAG4 and NcGRA1 epitopes construct) in BALB/c mice: the profile of the immune response and controlling the vertical transmission

Fernandes Fidelis,

Silva de Araújo,

Prates-Patarroyo

et al. 2023

Parasitol Res

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Neospora caninum is an apicomplexan protozoan that causes neosporosis, which has a high economic impact on cattle herds with no available vaccine. During infection, the secretion of dense granules and the expression of surface antigens play an important role in hosting immunomodulation. However, some epitopes of those antigens are immunogenic, and using these fractions could improve the subunit antigens in vaccine design. This study evaluates the recombinant peptides rsNcGRA1 and rsNcSAG4 derived from NcGRA1 and NcSAG4 native antigens as vaccine candidates produced by a fermentative process in the yeast culture system of Komagataella phaffii strain Km71, confirmed by colony PCR, SDS-PAGE, and western blotting. The assay was conducted in BALB/c mice using the peptides at low (25 μg) and standard (50 μg) dosages in monovalent and combined administrations at three time points with saponin as an adjuvant assessing the immunogenicity by antibodies response and cytokine production. We challenge the females after pregnancy confirmation using 2 × 105 NC-1 tachyzoites previously propagated in Vero cells. We assessed the chronic infection in dams and vertical transmission in the offspring by PCR and histopathology. Mice, especially those immunised with combined peptides and monovalent rsNcGRA1 at a standard dose, controlling the chronic infection in dams with the absence of clinical manifestations, showed an immune response with induction of IgG1, a proper balance between Th1/Th2 cytokines and reduced vertical transmission in the pups. In contrast, dams inoculated with a placebo vaccine showed clinical signs, low-scored brain lesions, augmented chronic infection with 80% positivity, 31% mortality in pups, and 81% vertical transmission. These findings indicate that rsNcGRA1 peptides in monovalent and combined with rsNCSAG4 at standard dose are potential vaccine candidates and improve the protective immune response against neosporosis in mice.

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“…The murine model has been utilized for many years to isolate and characterize Neospora caninum strains (11). Despite being a wellstudied model that enhances our understanding of neosporosis, including infection, immune response, vertical transmission, and other parameters, it continues to be a valuable approach for replicating the bovine model (12)(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

New insights into phenotype and genotype relationships in Neospora caninum

Cabrera,

Berná,

López

et al. 2023

Front. Vet. Sci.

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The successful isolation of four new Neospora caninum strains from different regions and with different backgrounds (obtained from an abortion storm or congenitally infected and asymptomatic calves) allowed us previously to characterize natural isolates, finding differences in phenotype and microsatellites. Given the variability observed, we wondered in this work whether these differences had consequences in virulence, invasion and vertical transmission using cell cultures and murine neosporosis models. In addition, we performed the genomic analysis and SNP comparative studies of the NcURU isolates. The results obtained in this work allowed us to establish that NcURU isolates are of low virulence and have unique phenotypic characteristics. Likewise, sequencing their genomes has allowed us to delve into the genetic singularities underlying these phenotypes, as well as the common mutated genes. This work opens a new perspective for diagnostic purposes and formulating possible vaccines based on attenuated strains.

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Establishment of a model of Neospora caninum infection in pregnant mice

Cited by 7 publications

References 23 publications

Dysfunction, oxidative stress markers, and cytokine expression in the placentae of mice experimentally infected with Neospora caninum

Dysfunction, oxidative stress markers, and cytokine expression in the placentae of mice experimentally infected with Neospora caninum

Immunisation with Neospora caninum subunits rsNcSAG4 and rsNcGRA1 (NcSAG4 and NcGRA1 epitopes construct) in BALB/c mice: the profile of the immune response and controlling the vertical transmission

New insights into phenotype and genotype relationships in Neospora caninum

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