Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
J Infect Dis. 2011 Aug 1;204(3):363-71. doi: 10.1093/infdis/jir277.
Commensal symbionts may become pathogens upon escaping their habitat. In the gut, Bacteroides fragilis protects against colitis through induction of interleukin 10 (IL-10) by CD4(+) T cells. When intestinal integrity is disrupted, B. fragilis and colonic contents escape into the peritoneum, causing abscesses and bacteremia. Whether the virulence mechanisms employed by B. fragilis during infections differ from those employed for symbiosis during commensalism is unknown. We demonstrate T cell-independent IL-10 production in response to B. fragilis during its pathogenic interactions with the host, and demonstrate the ability of the whole organism to activate Toll-like receptor 2-mediated MyD88 signaling in macrophages. Upon challenge with B. fragilis, mortality rates and serum proinflammatory cytokine levels were higher among IL-10(-/-) mice than among wild-type mice. Deaths were due to exuberant proinflammatory responses, not increased bacterial burden. During infection or commensalism, induction of IL-10 by B. fragilis is critical to this microbe's interactions with the immune system.
共生共生体在逃离其栖息地后可能成为病原体。在肠道中,脆弱拟杆菌通过 CD4(+)T 细胞诱导白细胞介素 10(IL-10)来预防结肠炎。当肠道完整性被破坏时,脆弱拟杆菌和结肠内容物逃入腹膜腔,导致脓肿和菌血症。在感染过程中,脆弱拟杆菌所采用的毒力机制是否与共生过程中所采用的机制不同尚不清楚。我们证明了在与宿主的致病相互作用过程中,无需 T 细胞即可产生针对脆弱拟杆菌的 IL-10,并且证明了整个生物体在巨噬细胞中激活 Toll 样受体 2 介导的 MyD88 信号的能力。在受到脆弱拟杆菌攻击时,IL-10(-/-)小鼠的死亡率和血清促炎细胞因子水平高于野生型小鼠。死亡是由于过度的促炎反应,而不是细菌负荷增加。在感染或共生过程中,脆弱拟杆菌诱导 IL-10 的产生对于该微生物与免疫系统的相互作用至关重要。