Choteau Laura, Vancraeyneste Hélène, Le Roy Didier, Dubuquoy Laurent, Romani Luiginia, Jouault Thierry, Poulain Daniel, Sendid Boualem, Calandra Thierry, Roger Thierry, Jawhara Samir
INSERM U995/2, Université Lille Nord de France, 1 Place Verdun, 59000 Lille, France.
U995-LIRIC, Lille Inflammation Research International Center, University Lille2, 59000 Lille, France.
Gut Pathog. 2017 Feb 15;9:9. doi: 10.1186/s13099-017-0158-0. eCollection 2017.
Toll-like receptors (TLRs) are the major pattern recognition receptors that mediate sensing of a wide range of microorganisms. TLR2 forms heterodimers with either TLR1 or TLR6, broadening its ligand diversity against pathogens. TLR1, TLR2 and TLR6 have been implicated in the recognition of , an opportunistic fungal pathogen that colonizes the gastrointestinal tract. In this study, we explored whether the deficiency in TLR1, TLR2 or TLR6 impacts colonization and inflammation-associated colonic injury in the dextran sulfate sodium (DSS)-induced colitis in mice.
DSS treatment and challenge induced greater weight loss, worse clinical signs of inflammation, higher histopathologic scores, and increased mortality rates in TLR1 and TLR2 mice when compared to TLR6 and wild-type mice. The number of colonies in the stomach, colon and feces was decreased in TLR6 mice as compared to TLR2, TLR1 and wild-type mice. Interestingly, the population of in colonic luminal contents, intestinal permeability to FITC-dextran and cytokine expression were significantly increased in TLR1 and TLR2 mice, while they were decreased in TLR6 mice.
In contrast to TLR6, both TLR1 and TLR2 deficiencies increased intestinal inflammation, and the overgrowth of and populations in the colitis model, suggesting the involvement of TLR1 and TLR2 in epithelial homeostasis, and a role of TLR6 in increasing intestinal inflammation in response to pathogen-sensing.
Toll样受体（TLRs）是介导多种微生物感知的主要模式识别受体。TLR2与TLR1或TLR6形成异二聚体，扩大了其针对病原体的配体多样性。TLR1、TLR2和TLR6参与了对一种定殖于胃肠道的机会性真菌病原体的识别。在本研究中，我们探讨了TLR1、TLR2或TLR6的缺陷是否会影响右旋糖酐硫酸钠（DSS）诱导的小鼠结肠炎中该真菌的定殖以及与炎症相关的结肠损伤。
与TLR6和野生型小鼠相比，DSS处理和该真菌攻击在TLR1和TLR2基因敲除小鼠中诱导了更严重的体重减轻、更差的炎症临床症状、更高的组织病理学评分以及更高的死亡率。与TLR2、TLR1和野生型小鼠相比，TLR6基因敲除小鼠胃、结肠和粪便中的该真菌菌落数量减少。有趣的是，TLR1和TLR2基因敲除小鼠结肠腔内容物中的该真菌数量、肠道对异硫氰酸荧光素 - 葡聚糖的通透性以及细胞因子表达显著增加，而在TLR6基因敲除小鼠中则降低。
与TLR6相反，TLR1和TLR2的缺陷均增加了肠道炎症以及结肠炎模型中该真菌数量的过度生长，提示TLR1和TLR2参与上皮内稳态，而TLR6在响应病原体感知时增加肠道炎症中发挥作用。
