Alam M Samiul, Kuo Jennifer L, Ernst Peter B, Derr-Castillo Victoria, Pereira Marion, Gaines Dennis, Costales Matthew, Bigley Elmer, Williams Kristina
Immunobiology Branch, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Laurel, MD 20708.
Division of Comparative Pathology and Medicine, University of California, San Diego, 9500 Gilman Drive, MC 0612, San Diego, CA 92093-0612.
Sci Rep. 2014 Mar 27;4:4486. doi: 10.1038/srep04486.
Food-borne Salmonella spp., are a major cause of hospitalization and death. Adenosine, an important immune regulator of inflammation, limits tissue damage during infection. CD39 (nucleoside triphosphate dephosphorylase) combined with ecto-5'-nucleotidase (CD73) metabolizes ATP to adenosine. We studied the expressions of CD39 and CD73 in tissues, and T helper cells in mice after Salmonella infection and evaluated the role of CD73 in regulating immune responses and bacterial clearance in wild-type and CD73-deficient (CD73(-/-)) mice. Both CD39 and CD73 transcript levels declined in the infected wild-type mice. Compared to wild-type mice, tissues from infected CD73(-/-) mice had significantly higher expression of pro-inflammatory cytokines and reduced anti-inflammatory responses. CD73(-/-) mice were more resistant to infection and had a greater inflammatory responses and a significantly lower bacterial load in the liver compared to wild-type mice. Thus, CD73 expression attenuates inflammation during murine Salmonellosis and impairs immunity, leading to increased bacterial colonization and prolonged infection.
食源性沙门氏菌是导致住院和死亡的主要原因。腺苷作为炎症的重要免疫调节因子，可限制感染期间的组织损伤。CD39（核苷三磷酸二磷酸酶）与胞外5'-核苷酸酶（CD73）共同作用将ATP代谢为腺苷。我们研究了沙门氏菌感染后小鼠组织中CD39和CD73的表达以及T辅助细胞，并评估了CD73在野生型和CD73缺陷型（CD73(-/-)）小鼠中调节免疫反应和细菌清除的作用。感染后的野生型小鼠中CD39和CD73的转录水平均下降。与野生型小鼠相比，感染的CD73(-/-)小鼠组织中促炎细胞因子的表达明显更高，抗炎反应降低。与野生型小鼠相比，CD73(-/-)小鼠对感染更具抵抗力，炎症反应更强，肝脏中的细菌载量显著更低。因此，CD73的表达可减轻鼠伤寒期间的炎症并损害免疫力，导致细菌定植增加和感染持续时间延长。
