Pereira Milton, Tourlomousis Panagiotis, Wright John, P Monie Tom, Bryant Clare E
Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK.
Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, 120 Fulbourn Road, Cambridge CB1 9NL, UK.
Nat Commun. 2016 Sep 27;7:12874. doi: 10.1038/ncomms12874.
Interleukin-1β (IL-1β) is a proinflammatory cytokine required for host control of bacterial infections, and its production must be tightly regulated to prevent excessive inflammation. Here we show that caspase recruitment domain-containing protein 9 (CARD9), a protein associated with induction of proinflammatory cytokines by fungi, has a negative role on IL-1β production during bacterial infection. Specifically, in response to activation of the nucleotide oligomerization domain receptor pyrin-domain containing protein 3 (NLRP3) by Salmonella infection, CARD9 negatively regulates IL-1β by fine-tuning pro-IL-1β expression, spleen tyrosine kinase (SYK)-mediated NLRP3 activation and repressing inflammasome-associated caspase-8 activity. CARD9 is suppressed during Salmonella enterica serovar Typhimurium infection, facilitating increased IL-1β production. CARD9 is, therefore, a central signalling hub that coordinates a pathogen-specific host inflammatory response.
白细胞介素-1β（IL-1β）是宿主控制细菌感染所需的促炎细胞因子，其产生必须受到严格调控以防止过度炎症。我们在此表明，含半胱天冬酶招募结构域蛋白9（CARD9），一种与真菌诱导促炎细胞因子相关的蛋白，在细菌感染期间对IL-1β的产生起负性作用。具体而言，在鼠伤寒沙门氏菌感染激活含吡喃结构域的核苷酸寡聚化结构域受体蛋白3（NLRP3）后，CARD9通过微调前体IL-1β表达、脾酪氨酸激酶（SYK）介导的NLRP3激活以及抑制炎性小体相关的半胱天冬酶-8活性来负性调节IL-1β。在鼠伤寒沙门氏菌感染期间CARD9受到抑制，从而促进IL-1β产生增加。因此，CARD9是协调病原体特异性宿主炎症反应的核心信号枢纽。
