Table_1_Mycoplasma hyopneumoniae Infection Activates the NOD1 Signaling Pathway to Modulate Inflammation.xlsx

Mycoplasma hyopneumoniae is a highly contagious pathogen causing porcine enzootic pneumonia, which elicits prolonged inflammatory response modulated by pattern recognition receptors (PRRs). Although significant advances have been achieved in understanding the Toll-Like receptors that recognize M. hyopneumoniae, the role of nucleotide-binding oligomerization domain 1 (NOD1) in M. hyopneumoniae infected cells remains poorly understood. This study revealed that M. hyopneumoniae activates the NOD1-RIP2 pathway and is co-localized with host NOD1 during infection. siRNA knockdown of NOD1 significantly impaired the TRIF and MYD88 pathway and blocked the activation of TNF-α. In contrast, NOD1 overexpression significantly suppressed M. hyopneumoniae proliferation. Furthermore, we for the first time investigated the interaction between M. hyopneumoniae mhp390 and NOD1 receptor, and the results suggested that mhp390 and NOD1 are possibly involved in the recognition of M. hyopneumoniae. These findings may improve our understanding of the interaction between PRRs and M. hyopneumoniae and the function of NOD1 in host defense against M. hyopneumoniae infection.

猪肺炎支原体（Mycoplasma hyopneumoniae）是一种高传染性病原体，可引发猪地方性肺炎，并诱导由模式识别受体（pattern recognition receptors, PRRs）调控的持续性炎症应答。尽管目前在解析识别猪肺炎支原体的Toll样受体（Toll-Like receptors）方面已取得显著进展，但核苷酸结合寡聚化结构域1（nucleotide-binding oligomerization domain 1, NOD1）在猪肺炎支原体感染细胞中的作用仍未得到充分阐明。本研究发现，猪肺炎支原体可激活NOD1-RIP2通路，并在感染过程中与宿主NOD1发生共定位。通过小干扰RNA（small interfering RNA, siRNA）敲低NOD1的表达，可显著削弱TRIF与MYD88通路的活性，并阻断肿瘤坏死因子-α（tumor necrosis factor-α, TNF-α）的激活。与之相反，NOD1过表达可显著抑制猪肺炎支原体的增殖。此外，本研究首次探究了猪肺炎支原体mhp390与NOD1受体之间的相互作用，结果显示mhp390与NOD1可能参与猪肺炎支原体的识别过程。上述研究结果有助于深化我们对模式识别受体与猪肺炎支原体之间相互作用，以及NOD1在宿主抵御猪肺炎支原体感染的免疫防御功能中的认知。