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Neospora caninum infection during early pregnancy in cattle: how the isolate influences infection dynamics, clinical outcome and peripheral and local immune responses.

ABSTRACT: This work studies the influence of Neospora caninum intra-species diversity on abortion outcome, infection dynamics in terms of parasite dissemination and peripheral-local immune responses in pregnant cattle. Animals were intravenously inoculated at day 70 of pregnancy with 10? tachyzoites of two isolates showing marked differences in virulence in vitro and in pregnant mouse models: Nc-Spain7, a high virulence isolate, and Nc-Spain8, a low-to-moderate virulence isolate. After inoculation, pregnancy was monitored, and dams were culled when foetal death was detected. Foetal mortality occurred in all infected heifers between days 24 and 49 post-infection (pi), however, it was detected sooner in Nc-Spain7-infected animals (median day?=?34) than those inoculated with Nc-Spain8 (median day?=?41) with a trend towards significance (P?

SUBMITTER: Regidor-Cerrillo J

PROVIDER: S-EPMC3922688 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Neospora caninum infection during early pregnancy in cattle: how the isolate influences infection dynamics, clinical outcome and peripheral and local immune responses.

Regidor-Cerrillo Javier J Arranz-Solís David D Benavides Julio J Gómez-Bautista Mercedes M Castro-Hermida José Antonio JA Mezo Mercedes M Pérez Valentín V Ortega-Mora Luis Miguel LM González-Warleta Marta M

Veterinary research 20140130

This work studies the influence of Neospora caninum intra-species diversity on abortion outcome, infection dynamics in terms of parasite dissemination and peripheral-local immune responses in pregnant cattle. Animals were intravenously inoculated at day 70 of pregnancy with 10⁷ tachyzoites of two isolates showing marked differences in virulence in vitro and in pregnant mouse models: Nc-Spain7, a high virulence isolate, and Nc-Spain8, a low-to-moderate virulence isolate. After inoculation, pregna ...[more]

PMID: 24479988

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Project description:IntroductionNeospora caninum is an important cause of abortion in cattle worldwide. Infection in cattle occurs horizontally by ingestion of oocysts shed by canids or vertically, from an infected dam to the fetus, and may result in abortion, stillbirth, or birth of seropositive offspring. The control of bovine neosporosis is difficult and costly. The objectives of this study were to estimate the current nationwide seroprevalence of N. caninum infections in Swiss cattle and to assess risk factors for infection with this parasite.MethodsWe conducted a cross-sectional study with cattle farms randomly selected and stratified according to population size, resulting in a sample of 780 female cattle. The cattle originated from 161 farms distributed over all Switzerland. The serum samples were tested for antibodies against N. caninum using a commercial ELISA and if inconclusive, retested using an in-house immunoblot technique. To collect farm parameters relevant to N. caninum transmission and prevention, farm owners were mailed a questionnaire which addressed topics putatively related to N. caninum infection such as husbandry, history of abortion, and presence of dogs on farm. Univariate analysis by generalized linear mixed model (with animal seropositivity as outcome variable) and logistic regression modeling (with farm seropositivity as outcome variable) was conducted on farm parameters investigated in the questionnaire.ResultsBy ELISA and immunoblot, 4.2% (33/780) of cattle sera yielded positive results. At the farm level, 16.2% (26/161) of the sampled farms had at least one seropositive animal. The return rate of the valid questionnaires was 54.0%. At the animal level, odds for farm seropositivity were 3.8 times higher when rodents had been recorded by the farmer as a problem on the farm. At the farm-level, two protective factors were identified: rearing of replacement heifers and feeding of concentrated feed.ConclusionWe recorded a low seroprevalence of N. caninum in a random sample of Swiss cattle representative for the years 2017-2018. Based on a questionnaire survey, we could identify risk and protective factors for infection with N. caninum, however their biological relevance needs to be confirmed in further studies.

Project description:BackgroundNeospora caninum is an obligate intracellular parasite, and its ability to survive inside host immune cells may be a key mechanism for the establishment of infection in cattle. In vitro studies carried out by our group have shown that N. caninum is able to replicate in bovine macrophages (MØs), alter their microbicidal mechanisms and exploit their motility. Furthermore, host-cell control seems to be isolate virulence-dependent.MethodsTo investigate the molecular basis underlying the innate responses in MØs against N. caninum and the mechanisms of parasite manipulation of the host cell environment, the transcriptome profile of bovine monocyte-derived MØs infected with high-virulence (Nc-Spain7) or low-virulence (Nc-Spain1H) N. caninum isolates was studied.ResultsFunctional enrichment revealed upregulation of genes involved in chemokine signalling, inflammation, cell survival, and inhibition of genes related with metabolism and phagolysosome formation. MØs activation was characterized by the induction of a predominantly M1 phenotype with expression of TLR2, TLR3 and TLR9 and activation of the NF-ƙB signalling pathway. Heat-killed N. caninum tachyzoites failed to activate NF-ƙB, and to inhibit lysosomal activity and apoptosis, which indicates active modulation by the parasite. The FoxO signalling pathway, Th1-Th2 differentiation, glycosaminoglycan degradation and apoptosis were pathways enriched only for low virulent Nc-Spain1H infection. In addition, Nc-Spain1H infection upregulated the IL12A and IL8 pro-inflammatory cytokines, whereas IL23 was downregulated by high virulent Nc-Spain7.ConclusionsThis study revealed mechanisms implicated in the recognition of N. caninum by bovine MØs and in the development of the subsequent immune response. NF-ƙB seems to be the main signalling pathway implicated in the pro-inflammatory bovine MØs response against this pathogen. Apoptosis and phagolysosome maturation are processes repressed by N. caninum infection, which may guarantee its intracellular survival. The results also indicate that Nc-Spain7 may be able to partially circumvent the pro-inflammatory response whereas Nc-Spain1H induces a protective response to infection, which may explain the more efficient transmission of the high-virulence Nc-Spain7 isolate observed in vivo.

Dataset Information

Neospora caninum infection during early pregnancy in cattle: how the isolate influences infection dynamics, clinical outcome and peripheral and local immune responses.

Publications

Neospora caninum infection during early pregnancy in cattle: how the isolate influences infection dynamics, clinical outcome and peripheral and local immune responses.

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