T-2 Toxin Exploits Gut-Derived Staphylococcus Saprophyticus to Disrupt Hepatic Macrophage Homeostasis

Area of Science:

• Immunology
• Toxicology
• Microbiology

Background:

• T-2 toxin, a prevalent mycotoxin in food and feed, poses health risks.
• Staphylococcus saprophyticus (S. saprophyticus) is an opportunistic pathogen with unknown pathogenic mechanisms.
• The interplay between mycotoxins, opportunistic pathogens, and host immunity is poorly understood.

Purpose of the Study:

• To investigate the effect of T-2 toxin on intestinal S. saprophyticus.
• To elucidate the mechanisms by which T-2 toxin-induced S. saprophyticus impacts liver immunity.
• To identify potential therapeutic strategies for mitigating T-2 toxin-induced liver damage.

Main Methods:

• Utilized piglet and mouse models exposed to sub-cytotoxic doses of T-2 toxin.
• Analyzed bacterial proliferation, translocation, and host immune responses in the liver.
• Investigated signaling pathways including NOD2, LC3, and CCL2 in Kupffer cells and hepatic macrophages.
• Assessed the efficacy of xylo-oligosaccharides and antibacterial agents in modulating gut microbiota and liver immunity.

Main Results:

• T-2 toxin promoted intestinal S. saprophyticus proliferation and translocation to the liver.
• Translocated S. saprophyticus activated NOD2-mediated pathways in Kupffer cells, inducing autophagy and monocyte recruitment.
• Hepatic macrophages underwent M1 polarization, indicating an inflammatory state.
• Xylo-oligosaccharides effectively restored hepatic macrophage homeostasis, unlike antibacterial agents.

Conclusions:

• S. saprophyticus plays a critical role in T-2 toxin-induced liver immune dysfunction.
• This study reveals a novel interaction between mycotoxins, opportunistic pathogens, and immune homeostasis.
• Targeting the gut microbiota with prebiotics like xylo-oligosaccharides may offer a therapeutic approach.