Role of a fluid-phase PRR in fighting an intracellular pathogen: PTX3 in Shigella infection

Shigella spp. are pathogenic bacteria that cause bacillary dysentery in humans by invading the colonic and rectal mucosa where they induce dramatic inflammation. Here, we have analyzed the role of the soluble PRR Pentraxin 3 (PTX3), a key component of the humoral arm of innate immunity. Mice that had been intranasally infected with S. flexneri were rescued from death by treatment with recombinant PTX3. In vitro PTX3 exerts the antibacterial activity against Shigella, impairing epithelial cell invasion and contributing to the bactericidal activity of serum.PTX3 is produced upon LPS-TLR4 stimulation in accordance with the lipid A structure of Shigella. In the plasma of infected patients, the level of PTX3 amount only correlates strongly with symptom severity. These results signal PTX3 as a novel player in Shigella pathogenesis and its potential role in fighting shigellosis. Finally, we suggest that the plasma level of PTX3 in shigellosis patients could act as a biomarker for infection severity.

志贺菌属（Shigella spp.）是一类致病菌，可通过侵袭人类结肠与直肠黏膜引发细菌性痢疾，并在此处诱发剧烈炎症反应。本研究针对可溶性模式识别受体（pattern recognition receptor, PRR）五聚蛋白3（Pentraxin 3, PTX3）的功能展开分析，该蛋白是固有免疫体液通路的关键组成部分。经鼻感染福氏志贺菌（S. flexneri）的小鼠经重组PTX3治疗后可免于死亡。体外实验证实，PTX3可发挥抗志贺菌活性，削弱上皮细胞侵袭能力，并辅助血清的杀菌活性。PTX3的产生依赖于脂多糖-Toll样受体4（LPS-TLR4）通路的刺激，且其诱导水平与志贺菌的脂质A结构相匹配。在感染患者的血浆中，PTX3水平仅与症状严重程度显著相关。上述结果表明，PTX3是志贺菌致病机制中的全新调控因子，同时在对抗志贺菌病的过程中具备潜在作用。最后，本研究提出，志贺菌病患者血浆中的PTX3水平可作为感染严重程度的生物标志物。