From Signaling Pathways to Distinct Immune Responses: Key Factors for Establishing or Combating Neospora caninum Infection in Different Susceptible Hosts

Abstract

: Neospora caninum is an intracellular protozoan parasite affecting numerous animal species. It induces significant economic losses because of abortion and neonatal abnormalities in cattle. In case of infection, the parasite secretes numerous arsenals to establish a successful infection in the host cell. In the same context but for a different purpose, the host resorts to different strategies to eliminate the invading parasite. During this battle, numerous key factors from both parasite and host sides are produced and interact for the maintaining and vanishing of the infection, respectively. Although several reviews have highlighted the role of different compartments of the immune system against N. caninum infection, each one of them has mostly targeted specific points related to the immune component and animal host. Thus, in the current review, we will focus on effector molecules derived from the host cell or the parasite using a comprehensive survey method from previous reports. According to our knowledge, this is the first review that highlights and discusses immune response at the host cell-parasite molecular interface against N. caninum infection in different susceptible hosts.

Keywords: Neospora caninum; immunity; infection; neosporosis; signaling pathways.

Figure 1

Possible pathways of interaction of Neospora caninum tachyzoite or derived molecules and host immune effectors. Cases of infection with N. caninum tachyzoites or parasite molecules (e.g., NcGPI, NcGRA6, NcGRA7, or NcCyp), are uptaken by macrophages or dendritic cells as professional antigen-presenting cells. This recognition is mediated by recognition receptors that are either transmembrane like most toll-like receptors (TLR) or cytosolic like nucleotide oligomerization domain (NOD)-like receptors. Afterwards, activation of host signaling pathways such as NF-kB is occurred to stimulate immune responses. In cases of N. caninum infection, proinflammatory cytokines as interleukin (IL)-6 and IL-12 are secreted, which subsequently enhance other immune cells to perform more potent and specialized effects. T-helper cells exert this role by producing IFN-γ which is a key molecule in combating N. caninum infection. Damage of the infected cells can be performed by cytotoxic T-cells or natural killer cells. Production of specific antibodies by B cells also plays a role in relieving subsequent infection by antibody binding to extracellular parasites.