Cellular immune responses in cattle experimentally infected with Neospora caninum.
ABSTRACT Neospora caninum has recently been identified as an important cause of infectious abortion in cattle. The parasite is closely related to Toxoplasma gondii, but the two species are antigenically distinct. To examine cell proliferative responses and the induction of IFN-gamma in experimentally infected cattle, four 2-4 months old calves were subcutaneously inoculated with N. caninum tachyzoites. Peripheral blood mononuclear cells were collected regularly and stimulated in vitro with a crude lysate of N. caninum or T. gondii tachyzoites. Significant proliferative responses to N. caninum antigen were recorded in all calves from days 4-6 postinoculation. This response was accompanied by production of high levels of IFN-gamma. Although the calves remained seronegative to T. gondii, while seroconverting to N. caninum, stimulation with T. gondii lysate resulted in cell proliferation of a similar magnitude as that obtained using the N. caninum lysate. However, the T. gondii lysate appeared less effective than the N. caninum lysate to stimulate IFN-gamma production. Cells taken from uninfected control animals did not show any significant proliferation to either N. caninum or T. gondii antigen and no IFN-gamma was produced. These results suggest that the two parasites may possess cross-reacting T-cell epitopes, but that the T cells specific for N. caninum may have a different functional capacity. This highlights the need to investigate the antigen specificity and cytokine profile of T cells from infected animals to help understand their role in immunity to N. caninum.
- [show abstract] [hide abstract]
ABSTRACT: To estimate the minimum rate of abortion attributable to infection with Neospora sp in selected California dairy herds. Prospective study. Twenty-six dairy herds containing 19,708 cows were studied. Fourteen herds had a history of abortions attributable to neosporosis, and 12 were herds in which neosporosis had not been identified as a cause of abortions. During a 1-year period, all available aborted fetuses were submitted to veterinary diagnostic laboratories to determine the cause of abortion. Reproductive records of cows that aborted were reviewed. Neospora sp infection was the major cause of abortion identified (113/266 abortions, 42.5%). The majority (232/266, 87.2%) of the aborted fetuses were submitted from herds with a history of abortions attributable to neosporosis, and Neospora sp infection was identified as the causative agent in 101 of 232 (43.5%) of the abortions from these herds. Fewer aborted fetuses were submitted from the 12 herds that did not have a history of abortion attributable to Neospora sp; however, neosporosis was confirmed as a cause of abortion in 6 of these 12 herds and was identified as the causative agent in 12 of 34 (35.3%) abortions from these herds. The disease was widespread throughout the state (19/26 herds in our study). Available reproductive histories of cows that had abortions attributed to neosporosis were evaluated, and 4 cows were identified that twice aborted Neospora-infected fetuses. Abortion attributable to Neospora sp infections can be expected to be a continuing major cause of abortion in dairy herds with a history of neosporosis as well as in dairy herds that have a history of sporadic abortions, but for which Neospora sp infections have not been previously identified as a cause of abortion. Subsequent pregnancies in cows that abort a Neospora sp-infected fetus also are at risk of infection, suggesting that the immunity provided by an initial infection is inadequate to prevent repeat infection or that cows can be persistently infected with Neospora sp.Journal of the American Veterinary Medical Association 12/1995; 207(9):1206-10. · 1.72 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Parasitic infection is frequently accompanied by a downregulation in host cell-mediated immunity. Recent studies suggest that this modulation of helper T cells and effector cell function can at least in part be attributed to the action of a set of inhibitory cytokines produced by T lymphocytes as well as by a number of other cell types. The best characterized of these inhibitory lymphokines are IL-4, IL-10 and TGF-beta. Interestingly, both IL-4 and IL-10 are produced by the Th2 but not the Th1 subset of CD4+ helper cells. The former subset dominates in many situations of chronic or exacerbated parasitic infection and is thought to suppress Th1 function as a consequence of the cross-regulatory activity of these two cytokines. The latter hypothesis is supported by recent experiments demonstrating that mAb-mediated neutralization of IL-10 reverses suppressed IFN-gamma responses and/or disease susceptibility in mice with parasitic infections. In vivo neutralization of TGF-beta has also been reported to increase host resistance to parasite challenge. In addition to suppressing T-cell differentiation, function or proliferation, IL-4, IL-10 and TGF-beta each inhibit the ability of IFN-gamma to activate macrophages for killing of both intracellular and extracellular parasites. Moreover, the three cytokines are able to synergize with each other in downregulating these parasiticidal effects. Interestingly, each of the cytokines inhibits the production of reactive nitrogen oxides, an effector mechanism previously demonstrated to play a major role in parasite killing by activated macrophages. In the case of IL-10, this suppression of nitrogen oxide production appears to result from an inhibition of TNF-alpha synthesis leading to defective macrophage stimulation. While distant from parasites in their biology and phylogeny, some retroviruses also appear to induce an over-production in downregulatory cytokines which is closely associated with the onset of immunodeficiency. Thus, in an animal model involving infection of mice with LP-BM5 MuLV and in human HIV infection, Th2 (IL-10 and/or IL-4) cytokine synthesis is increased while Th1 (IFN-gamma and/or IL-2) cytokine production is suppressed. These observations suggest that cytokine-mediated cross-regulation may play a role in the pathogenesis of acquired immune deficiency disease, contributing both to the progression of retroviral infection and the increase in susceptibility to opportunistic infections and malignancy. Observations of similar cytokine cross-regulatory activities in organisms as diverse as helminths, protozoa and retroviruses predict that comparable mechanisms may operate in a wide variety of infectious diseases.Immunological Reviews 07/1992; 127:183-204. · 12.16 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Neospora caninum infection was diagnosed in 5 young dogs from 2 litters with a common parentage. The pups were born healthy, but developed hind limb paresis 5 to 8 weeks after birth. The predominant lesions were polyradiculoneuritis and granulomatous polymyositis. Neospora caninum was seen microscopically in sections of naturally infected pups, and was isolated in cell cultures, mice, and dogs inoculated with infected canine tissues. Antibodies to N caninum were detected in sera of infected dogs by indirect fluorescent antibody test.Journal of the American Veterinary Medical Association 12/1988; 193(10):1259-63. · 1.72 Impact Factor