Differential Responses of Bovine Monocyte-Derived Macrophages to Infection by Neospora caninum Isolates of High and Low Virulence

Abstract

Neospora caninum , a protozoan parasite closely related to Toxoplasma gondii , represents one of the main causes of abortion in cattle. Macrophages (MØs) are mediators of the innate immune response against infection and likely one of the first cells encountered by the parasite during the host infection process. In this study, we investigated in vitro how high or low virulent isolates of N. caninum (Nc-Spain7 and Nc-Spain1H, respectively) interact with bovine monocyte-derived MØs and the influence of the isolate virulence on the subsequent cellular response. Both isolates actively invaded, survived and replicated in the MØs. However, Nc-Spain7 showed a higher invasion rate and a replication significantly faster, following an exponential growth model, whereas Nc-Spain1H presented a delayed replication and a lower growth rate without an exponential pattern. N. caninum infection induced a hypermigratory phenotype in bovine MØs that was characterized by enhanced motility and transmigration in vitro and was accompanied by morphological changes and abrogated extracellular matrix degradation. A significantly higher hypermotility was observed with the highly virulent isolate Nc-Spain7. Nc-Spain1H-infected MØs showed elevated reactive oxygen species (ROS) production and IL12p40 expression, which also resulted in increased IFN-γ release by lymphocytes, compared to cells infected with Nc-Spain7. Furthermore, IL-10 was upregulated in MØs infected with both isolates. Infected MØs exhibited lower expression of MHC Class II, CD86, and CD1b molecules than uninfected MØs, with non-significant differences between isolates. This work characterizes for the first time N. caninum replication in bovine monocyte-derived MØs and details isolate-dependent differences in host cell responses to the parasite.

Characterization of dendritic cells and follicular dendritic cells in the hepatic lymph nodes and liver of sheep experimentally infected with Fasciola hepatica

“…infection of human monocyte-derived dendritic cells resulted in reduced expression of CD1b [52]. Similar results were found in bovine monocyte-derived macrophages infected with Neospora caninum [53]. These results contrast with those found in the present study, in which the number of CD1b+ DC increased significantly in HLNs and livers at 18 dpi compared to that in the UC group.…”

“…The difference in the expression of CD1b in the two parasites may be related to differences in the host response to N. caninum and F. hepatica infections in cattle and sheep, respectively. Thus, in N. caninum-infected cattle, elevated reactive oxygen species (ROS), IL-10 and IFN-γ production has been reported [53], whereas in F. hepatica-infected sheep, decreased ROS production [54] and decreased IFN-γ gene expression have been observed [15].…”

The unicellular eukaryotic parasite Toxoplasma gondii hijacks the migration machinery of mononuclear phagocytes to promote its dissemination

“…In mice, adoptively transferred parasitised DCs confer exacerbated dissemination with elevated parasite loads (Lambert et al, 2006;Fuks et al, 2012;Kanatani et al, 2017). Hypermigratory responses of mononuclear phagocytes (DCs, monocytes, macrophages, microglia) appear to be a conserved feature across host species (human, mouse, bovine) and are also induced by the related coccidian Neospora caninum (Collantes-Fernandez et al, 2012;Garcia-Sanchez et al, 2019). Yet, while hypermigration in DCs/monocytes/macrophages/microglia is induced by all T. gondii and N. caninum strains tested to date, measurable differences exist between parasite strains/lineages in the magnitude of induction of the hypermigratory phenotype, as defined in vitro.…”

Crosstalk between Neospora caninum and the bovine host at the maternal-foetal interface determines the outcome of infection

“…Previously, we used in vitro and in vivo models to characterize two N. caninum isolates with marked differences in virulence: Nc-Spain7 and Nc-Spain1H, previously classified as high-and lowvirulence isolates, respectively [6][7][8]. Specifically, in bovine trophobast cells [9][10][11] and macrophages [12], Nc-Spain7 showed an increased infection and proliferation rates, whereas Nc-Spain1H displayed a reduced proliferation associated to a higher stimulation of immune responses. However, in vitro models cannot mimic the complex architecture of the bovine placenta, as they lack the microenvironmental influences and the host ability to compensate for stress conditions.…”