TNF-TNFR1 Signaling Enhances the Protection Against Neospora caninum Infection

Abstract

Neospora caninum is a protozoan associated with abortions in ruminants and neuromuscular disease in dogs. Classically, the immune response against apicomplexan parasites is characterized by the production of proinflammatory cytokines, such as IL-12, IFN-γ and TNF. TNF is mainly produced during the acute phases of the infections and binds to TNF receptor 1 (CD120a, p55, TNFR1) activating a variety of cells, hence playing an important role in the induction of the inflammatory process against diverse pathogens. Thus, in this study, we aimed to evaluate the role of TNF in cellular and humoral immune responses during N. caninum infection. For this purpose, we used a mouse model of infection based on wildtype (WT) and genetically deficient C57BL/6 mice in TNFR1 (Tnfr1-/-). We observed that Tnfr1-/- mice presented higher mortality associated with inflammatory lesions and increased parasite burden in the brain after the infection with N. caninum tachyzoites. Moreover, Tnfr1-/- mice showed a reduction in nitric oxide (NO) levels in vivo. We also observed that Tnfr1-/- mice showed enhanced serum concentration of antigen-specific IgG2 subclass, while IgG1 production was significantly reduced compared to WT mice, suggesting that TNFR1 is required for regular IgG subclass production and antigen recognition. Based on our results, we conclude that the TNF-TNFR1 complex is crucial for mediating host resistance during the infection by N. caninum.

Temporal transcriptomic changes in microRNAs involved in the host immune response and metabolism during Neospora caninum infection

“…Furthermore, downregulated miR-361-3p was predicted to regulate the expression of MAP3K8 through the TNF signaling pathway in our study, and MAP3K8 has been reported to promote angiogenesis and inhibit inflammation with the participation of the tumor necrosis factor-α (TNF-α) signaling pathway [ 64 ]. Interestingly, C57BL/6 mice infected with N. caninum exhibited higher mortality associated with inflammatory lesions and increased parasite burden in the brain through TNF-TNFR1 signaling [ 65 ]. In addition, in our study, downregulated miR-128-5p was predicted to activate MKNK2 through the MAPK signaling pathway.…”