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 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, 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 < 0.11). Similar histological lesions were observed in placentomes and in most of the foetuses from the two infected groups. However, parasites were more frequently detected in the placenta and foetuses by PCR and in the foetal brain by immunohistochemistry in Nc-Spain7-infected animals. Specific antibodies were detected starting at day 13 post-infection in all infected cattle, with higher IgG levels in Nc-Spain7-infected group. IFN-γ and IL-4 profiles also varied between infected groups in PBMC stimulation assays. Infected animals showed significant increases in their cytokine mRNA levels (IFN-γ, IL-4, IL-10, IL-12p40 and TNF-α) in the caruncle at time of foetal death. Differences between the infected groups were also observed for cytokine profiles. These results demonstrate the influence of the N. caninum isolate on foetal death outcome, infection dynamics and immune responses in cattle.

Markers related to the diagnosis and to the risk of abortion in bovine neosporosis

“…Similar results have been reported in the placenta in naturally infected cattle (Rosbottom et al, 2011). The mixed pattern of up-regulation of cytokines in Neosporainfection has also been observed in several studies in experimental infections in both aborted and non-aborted dams at early pregnancy infections (Regidor-Cerrillo et al, 2014;Rosbottom et al, 2007Rosbottom et al, , 2008; at 110 days of gestation (Almería et al, 2003; or at 210 days of gestation (Bartley et al, 2013). Recently, Cantón et al (2014) observed a milder Th1 immune response based on infiltration of cytokine expressing cells in the placenta during later stages of gestation following Nc-1 infection that could partially explain the less severe clinical outcome when compared to early pregnancy.…”

“…There have been few studies comparing different isolates in vivo (Caspe et al, 2012;Chryssafidis et al, 2014;Regidor-Cerrillo et al, 2014) Regidor-Cerrillo et al (2014 compared two isolates, Nc-Spain7, a high virulence isolate, and NcSpain8, a low-to-moderate virulence isolate on heifers. Although all infected heifers suffered abortion when inoculated early in pregnancy, abortion occurred earlier in those inoculated with Nc-Spain7-infected animals with the parasite being more frequently detected in the placenta and fetuses.…”

Two Novel Calcium-Dependent Protein Kinase 1 Inhibitors Interfere with Vertical Transmission in Mice Infected with Neospora caninum Tachyzoites

“…In this model, which uses the N. caninum Spain7 (Nc-Spain7) isolate, which is highly virulent in vitro and in vivo in mice (21,22) as well as in sheep (23), all pups of infected dams died within 3 weeks; pups of noninfected dams survived. Thus, the model is reproducible, as shown in several recent studies (17,20,24).…”

Regulator Versus Effector Paradigm: Interleukin-10 as Indicator of the Switching Response

“…Similarly to DCs, effector CD8+ T cell response is inhibited during H5N1 viral infection by IL-10 producing CD8+ Treg cells [75,76]. The induced manipulation toward the Th2 profile assures increased surviving possibility for different infective agents, such as viruses, chlamydias, and parasites [65, 67-69, 73,74,[77][78][79]. The early IL-10 production by T cell, B cell, and monocyte/macrophage (but not on NK and DC) activation can lead to chronicity of lymphocytic choriomeningitis and B hepatitis virus infections, and the IL-10-mediated early T cell Similarly to viral infections, parasite-induced IL-10 production by various immune cells is associated with impaired resistance to protozoan and nematodes [80,81,86,87].…”