Background: Mycoplasma ovipneumoniae (M. ovi) is the causal pathogen of chronic non-progressive pneumonia infections in sheep, goats, bighorn, and wild small ruminants. However, the mechanism of infection and immune response to M. ovi remain unclear. Invading microbes express lipid-associated membrane proteins (LAMPs) on the cell surface that interact with host cells to facilitate infection, and are thus the major molecules recognised by the host immune system. Upon LAMP recognition, Tolllike receptor 2 (TLR2) and NLRP3 inflammasome sense the pathogens and signalling pathways for cytokine secretion. In this study, we investigated whether M. ovi and M. ovi-derived LAMPs are immunobiologically active compounds capable of activating mouse peritoneal macrophages and explored the underlying mechanism.Results: After infection of wild-type mice with M. ovi, the expression of TLR2 and NLRP3 at the transcription and translational levels was determined with reverse transcription-polymerase chain reaction and flow cytometry. In addition, the cytokine levels and associated pathways were detected in infected wild-type, Tlr2 -/-, and Nlrp3 -/mice via enzyme-linked immunosorbent assaying and western blotting. The nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) signalling pathways were found to mediate the expression of inflammatory cytokines in M. ovi or M. ovi-derived LAMPs-infected peritoneal macrophages, and cytokines were not induced in Tlr2 -/and/or Nlrp3 -/macrophages. Conclusion:Host cytokine production is activated in response to M. ovi-derived LAMPs through the NF-κB and MAPK signalling pathway via TLR2. BackgroundMycoplasmas are a well-studied heterogeneous group of small parasitic microorganisms that capable of self-replication, and are characterised by a wall-less envelope. These parasites cause numerous types of infections in humans and other mammals. Among these, Mycoplasma ovipneumoniae (M. ovi) causes a chronic non-progressive pneumonia infection in sheep, goats, bighorn, and wild small ruminants [1-4], which has resulted in a worldwide epidemic and enormous financial losses to the 4 sheep industry [2, 4, 5]. Despite extensive efforts to understand the mechanisms underpinning M. ovi infection, the molecular basis of macrophage responses to M. ovi infection remains largely unknown. Lipid-associated membrane proteins (LAMPs) are a mixture of bacterial lipoproteins expressed on the cell surface that act as the primary interacting structures with host cells [6]. LAMPs from several mycoplasmas have been demonstrated to be biologically active, and are considered to be the most potent initiators of inflammatory reactions in response to Mycoplasma infection [7-10]. Through direct interaction with the host cells, LAMPs can influence the functions of macrophages, monocytes, and brain astrocytes to trigger proinflammatory cytokine production or, in some cases, necrosis or apoptosis to evade the host immune response and facilitate infection [11]. Thus, gaining a better understanding of the Mycoplasma LAMP...