Miettinen Minja, Veckman Ville, Latvala Sinikka, Sareneva Timo, Matikainen Sampsa, Julkunen Ilkka
Department of Viral Diseases and Immunology, National Public Health Institute, Mannerheimintie 166, 00300 Helsinki, Finland.
J Leukoc Biol. 2008 Oct;84(4):1092-100. doi: 10.1189/jlb.1206737. Epub 2008 Jul 14.
Macrophages are phagocytes that recognize bacteria and subsequently activate appropriate innate and adaptive immune responses. TLRs are essential in identifying conserved bacterial structures and in initiating and mediating innate immune responses. In this work, we have characterized TLR gene expression in human monocyte-derived macrophages in response to stimulation with two live Gram-positive bacteria, a human commensal and probiotic Lactobacillus rhamnosus GG (LGG), and an important human pathogen Streptococcus pyogenes. LGG and S. pyogenes enhanced TLR2 expression in macrophages. LGG and S. pyogenes also required TLR2 for NF-kappaB activation. Only pathogenic S. pyogenes was able to up-regulate TLR3 and TLR7 gene expression. This up-regulation was dependent on IFN-alpha/beta, as neutralizing anti-IFN-alpha/beta antibodies reduced S. pyogenes-induced TLR3 and TLR7 mRNA expression. Our results show that despite similarities, TLR responses of macrophages differ for a Gram-positive probiotic and a pathogen. Our data suggest that macrophages can discriminate between probiotic and pathogenic bacteria by IFN-mediated TLR gene regulation.
巨噬细胞是能够识别细菌并随后激活适当的固有免疫和适应性免疫反应的吞噬细胞。Toll样受体（TLR）在识别保守的细菌结构以及启动和介导固有免疫反应方面至关重要。在这项研究中，我们已经对人单核细胞衍生的巨噬细胞中TLR基因的表达进行了表征，该巨噬细胞是在受到两种活的革兰氏阳性细菌刺激后产生的，一种是人体共生和益生菌鼠李糖乳杆菌GG（LGG），另一种是重要的人类病原体化脓性链球菌。LGG和化脓性链球菌增强了巨噬细胞中TLR2的表达。LGG和化脓性链球菌激活核因子κB（NF-κB）也需要TLR2。只有致病性化脓性链球菌能够上调TLR3和TLR7基因的表达。这种上调依赖于Ⅰ型干扰素（IFN-α/β），因为中和性抗IFN-α/β抗体可降低化脓性链球菌诱导的TLR3和TLR7 mRNA表达。我们的结果表明，尽管存在相似之处，但巨噬细胞对革兰氏阳性益生菌和病原体的TLR反应有所不同。我们的数据表明，巨噬细胞可以通过IFN介导的TLR基因调控来区分益生菌和病原菌。
