<b>Mechanisms of Immune Organ Injury and Immunosuppression during </b><b><i>Mycoplasma synoviae</i></b><b> Infection in Chickens</b>

Mycoplasma synoviae (MS) is an important avian pathogen in poultry, but how it disrupts immune organ development and homeostasis remains unclear. Here, we established an SPF chicken model spanning different stages of MS infection to investigate immune organ injury and immunosuppression. MS infection caused progressive growth retardation and marked atrophy of the thymus, spleen, and bursa of Fabricius. Persistent MS colonization in immune tissues was accompanied by declining immune organ indices, aggravated histopathological injury, and lymphocyte depletion. Oxidative DNA damage and lymphocyte apoptosis appeared early and became increasingly severe as infection progressed. Meanwhile, mitochondria dependent apoptotic signaling remained activated and ultimately led to caspase 3 mediated lymphocyte apoptosis. Although TLR4/NF-κB and MAPK signaling pathways were activated throughout infection, effective immune responses were not maintained, as indicated by discordance between the mRNA and protein expression of TNF-α, IL-1β, IL-6, and IL-10. In parallel, SOCS1, SOCS3, A20, and PD-1 were progressively upregulated. Collectively, these findings indicate that MS impairs immune organ development and suppresses immune function in chickens through oxidative injury, lymphocyte apoptosis, and activation of inhibitory immunoregulatory pathways.This study advances understanding of MS associated immunosuppression and supports improved control strategies.