Macrophage migration inhibitory factor favors Neospora caninum infection in mice
Vanessa Resende Souza Silva1, Caroline Martins Mota1, Lydiane Parreira Maia1
1Laboratório de Imunoparasitologia "Dr. Mario Endsfeldz Camargo", Brazil.
Abstract:
Neospora caninum is a protozoan parasite with worldwide incidence, acting as a major cause of reproductive failures in ruminants and neuromuscular symptoms in dogs. Macrophage Migration Inhibitory Factor (MIF) is produced by several cell types and exhibits a central role in immune responses against intracellular pathogens. The present study aimed to comprehend the role of MIF in the relationship between N. caninum and its host. We used in vivo, in vitro and ex vivo experiments in a model of infection based on genetically deficient mice to analyze the infection kinetics and inflammatory markers. MIF production was measured in response to N. caninum during the acute and chronic phases of the infection. While Mif-/- mice survived lethal doses of NcLiv tachyzoites, sublethal infections in these mice showed that parasite burden was controlled in target tissues, alongside with reduced inflammatory infiltrates detected in lung and brain sections. TNF was increased at the initial site of the infection in genetically deficient mice and the MIF-dependent reduction was confirmed in vitro with macrophages and ex vivo with primed spleen cells. In sum, MIF negatively regulated host immunity against N. caninum, favoring disease progression.
Insights
Macrophage Migration Inhibitory Factor (MIF) negatively impacts host immunity against Neospora caninum, a parasite causing reproductive issues in livestock and neurological problems in dogs. Eliminating MIF improved survival and controlled infection in mice.
Area of Science:
- Veterinary Parasitology
- Immunology
- Protozoan Infections
Background:
- Neospora caninum causes significant economic losses in livestock due to reproductive failure.
- Macrophage Migration Inhibitory Factor (MIF) plays a critical role in immune responses to intracellular pathogens.
- Understanding MIF's role in N. caninum infection is crucial for developing effective control strategies.
Purpose of the Study:
- To elucidate the role of Macrophage Migration Inhibitory Factor (MIF) in the host-parasite relationship with Neospora caninum.
- To analyze infection kinetics and inflammatory markers in a mouse model lacking MIF.
Main Methods:
- Infection of genetically modified Mif-/- mice with Neospora caninum tachyzoites.
- In vivo, in vitro, and ex vivo analyses of parasite burden, inflammatory infiltrates, and cytokine production (TNF).
- Assessment of survival rates and disease progression during acute and chronic infection phases.
Main Results:
- Mif-/- mice exhibited increased survival against lethal N. caninum doses.
- Sublethal infections in Mif-/- mice showed controlled parasite burden and reduced lung/brain inflammation.
- Tumor Necrosis Factor (TNF) levels were elevated at the infection site in Mif-/- mice, indicating enhanced early immune response.
Conclusions:
- MIF negatively regulates host immune responses against Neospora caninum.
- MIF deficiency enhances host resistance, controlling parasite dissemination and reducing inflammation.
- Targeting MIF could be a potential therapeutic strategy to combat N. caninum infections.
