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

Mycoplasma pneumonia is a chronic respiratory disease that seriously affects the health of sheep. To date, little information is available about the damage caused by Mycoplasma ovipneumoniae (MO) pneumonia to host lungs. Here, after sheep were infected with MO for 28 days, severe inflammatory reactions and pathological damage occurred. By using single-cell RNA sequencing (scRNA-seq), all the transcriptome changes in 11 cell types in sheep lung tissue were systematically analyzed, and the key biological processes regulating inflammation and immunity were identified. Moreover, we constructed both intercellular communication models and differential expression maps of key regulatory genes for each cell subgroup. We also specifically focused on the response of T cell subpopulations and neutrophils to MO infection. Long-term infection may affect an organism's immune response, inhibit intercellular communication, and highlight the important role of the cyclophilin A (CypA) and macrophage migration inhibitory factor (MIF) pathways in intercellular communication. Notably, MO infection decreased the toxicity of CD8 effector T cells and depleted regulatory T cells, thus inhibiting normal cell function. Subsequently, emphasis was placed on the important role of the neutrophil marker gene S100A9 in promoting neutrophil clearance of MO through activation of the ERK signaling pathway and reactive oxygen species (ROS) burst in vitro. These results contribute to understanding the progression of MO infection in the lungs and provide a rich database on the molecular basis of the response to different cell types in MO infection.