# The resistance to Toxoplasma gondii in Microtus fortis is associated with the activation of the complement lectin pathway

## TL;DR

Microtus fortis resists Toxoplasma gondii infection through a complement system activated via the lectin pathway, which helps destroy the parasite.

## Contribution

The study identifies the lectin pathway of the complement system as a novel mechanism for natural resistance to T. gondii in Microtus fortis.

## Key findings

- M. fortis exhibits high resistance to T. gondii RH strain and clears tachyzoites effectively.
- The complement system in M. fortis is activated via the lectin pathway to lyse T. gondii tachyzoites.
- Inhibiting the complement system in M. fortis significantly reduces its ability to clear the infection.

## Abstract

Toxoplasma gondii (T. gondii) is an intracellular parasite that infects nearly all warm-blooded animals, including humans. The susceptibility to T. gondii infection varies among hosts. In this study, we found that Microtus fortis (M. fortis) exhibited a naturally high level of resistance to the T. gondii RH strain, as evidenced by survival assays. We further observed that M. fortis activated the complement system via the lectin pathway to lyse T. gondii tachyzoites, whereas serum from Kunming (KM) mice showed no such effect. Furthermore, the ability of M. fortis to clear T. gondii tachyzoites was significantly impaired when the complement system was inhibited by cobra venom factor (CVF). These findings indicate that M. fortis exhibits a naturally high resistance to T. gondii. This resistance is mediated, in part, by the complement system, which is activated through the lectin pathway and directly lyses extracellular tachyzoites. Thus, the complement system plays an essential role in controlling T. gondii infection in this species.

T. gondii can infect nearly all warm-blooded animals. Mice infected with T. gondii type I strains typically develop acute toxoplasmosis symptoms and often succumb to the infection. However, we observed that M. fortis infected with the T. gondii type I strain did not develop acute toxoplasmosis and effectively cleared the T. gondii tachyzoites. Our study revealed that T. gondii tachyzoites activate the complement system in M. fortis via the lectin pathway, leading to their destruction by lysis. In contrast, the complement system in mice failed to eliminate the tachyzoites. Furthermore, complement inhibition in M. fortis significantly impaired its ability to clear the infection. These findings suggest that the complement system plays a critical role in enabling M. fortis to control T. gondii infection. The complement-mediated killing of T. gondii offers new insights for the development of anti-T. gondii drugs and vaccines.