Up Regulation of the Maternal Immune Response in the Placenta of Cattle Naturally Infected with Neospora caninum

Abstract

Neospora caninum is an intracellular protozoan parasite which is a major cause of abortion in cattle worldwide. It forms persistent infections which recrudesce during pregnancy leading to foetal infection and in a proportion of cases, abortion. The mechanisms underlying abortion are not understood. In this study, recrudescence of a persistent infection in eight naturally infected cows occurred between 20 and 33 weeks of gestation. Animals were killed at the time of recrudescence and parasites were detected in the placentae and foetuses. An active maternal immune response consisting of an infiltration of CD4+ and CD8+ T cells and a 46–49 fold increase in interferon-γ and interleukin-4 mRNA was detected. Other cytokines, notably interleukin-12 p40, interleukin-10 and tumour necrosis factor-α were also significantly increased and Major Histocompatibility Class II antigen was expressed on maternal and foetal epithelial and stromal fibroblastoid cells. Significantly, despite the presence of an active maternal immune response in the placenta, all the foetuses were alive at the time of maternal euthanasia. There was evidence of parasites within foetal tissues; their distribution was restricted to the central nervous system and skeletal muscle and their presence was associated with tissue necrosis and a non-suppurative inflammatory response involving lymphocytes and macrophages, irrespective of the gestational age of the foetus. Whilst an active maternal immune response to a pathogen in the placenta is generally considered to be damaging to the foetal trophoblast, our findings suggest that the presence of a parasite-induced maternal immune response in the placenta is not detrimental to foetal survival but may contribute to the control of placental parasitosis.

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

“…These results point to a partial protective immune response against the parasite related to the increased expression of IFN-γ and the increased presence of other cytokines such as IL-12 and IL-10, especially toward the end of pregnancy (Almería et al, 2012). 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).…”

Neosporosis in animals—The last five years

“…Extensive lesions in vital organs can directly kill the fetus . The production of regulatory cytokines (such as IL-10) and inflammatory (such as gamma interferon) cytokines, and a direct injury of the fetus by tachyzoites multiplication may determine the survival or death of the fetus (Innes, 2007;Rosbottom et al, 2007Rosbottom et al, , 2008Rosbottom et al, , 2011Almería et al, 2010;Almeria et al, in press). High levels of prolactin in Neospora infected cows may have a protective effect on gestation (Garcia-Ispierto et al, 2009).…”

Experimental Neospora caninum infection modifies trophoblast cell populations and plasma pregnancy-associated glycoprotein 1 and 2 dynamics in pregnant dairy heifers

“…However, this decline was transient and could be perhaps related to the recovery of lesions in the placenta, as indicated by Maley et al (2006). It also suggests that the presence of a parasite-induced, maternal immune response in the placenta may not be detrimental to foetal survival, and, rather, could help control the placental parasitosis (Rosbottom et al, 2011). Another explanation could be that increased PAG levels are the consequence of PAGs secreted by other binucleate cells in small cotyledons.…”