Mycoplasma ovipnuemoniae impairs the immune response of sheep and suppresses neutrophil function by inhibiting S100A9

Area of Science:

• Veterinary Pathology
• Immunology
• Genomics

Background:

• Mycoplasma ovipneumoniae (MO) causes chronic respiratory disease in sheep, with limited understanding of its lung pathology.
• Sheep infected with MO exhibit severe inflammation and tissue damage after 28 days.

Purpose of the Study:

• To systematically analyze transcriptome changes in sheep lung cells following MO infection.
• To identify key biological processes regulating inflammation and immunity in ovine pneumonia.
• To construct intercellular communication models and map gene expression in response to MO.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) of sheep lung tissue after 28 days of MO infection.
• Analysis of 11 distinct cell types to identify transcriptome alterations.
• Construction of intercellular communication networks and differential gene expression maps.

Main Results:

• MO infection induced severe inflammatory reactions and pathological damage in sheep lungs.
• scRNA-seq identified key regulatory genes and biological processes involved in immunity and inflammation.
• Intercellular communication pathways, including cyclophilin A (CypA) and macrophage migration inhibitory factor (MIF), were highlighted.
• MO infection impaired CD8 effector T cell toxicity and depleted regulatory T cells.
• Neutrophil function, mediated by S100A9, ERK signaling, and ROS, was crucial for MO clearance.

Conclusions:

• MO infection significantly impacts sheep lung immunity and intercellular communication.
• The study provides a molecular basis for understanding ovine pneumonia progression and host response.
• Insights into T cell subpopulations and neutrophil responses offer potential therapeutic targets.