Yakult Central Institute for Microbiological Research, Tokyo, Japan.
Immunology. 2009 Sep;128(1 Suppl):e858-69. doi: 10.1111/j.1365-2567.2009.03095.x.
We previously showed that Lactobacillus strains having a rigid cell wall resistant to intracellular digestion can stimulate macrophages to induce large a quantity of interleukin-12 (IL-12). In this study, we examined the influence of lactobacilli and bacterial cell wall components on IL-12 production by macrophages that was induced by Lactobacillus casei, which has a rigid cell wall. Easily digestible lactobacilli such as Lactobacillus johnsonii and Lactobacillus plantarum or their intact cell walls (ICWs) weakly or very weakly induced IL-12 production by macrophages, and inhibitedL. casei-induced IL-12 production. While the ICW of L. casei was resistant to intracellular digestion and did not inhibit L. casei-induced IL-12 production, its polysaccharide-depleted ICW, i.e. intact peptidoglycan, was sensitive to intracellular digestion and inhibited L. casei-induced IL-12 production. Furthermore, the peptidoglycans of L. johnsonii, L. plantarum and Staphylococcus aureus also inhibited L. casei-induced IL-12 production. Peptidoglycans from lactobacilli suppressed L. casei-induced expression of IL-12p40 but not IL-12p35 mRNA. Inhibition of IL-12 production by peptidoglycan was mitigated in Toll-like receptor 2 (TLR2)-deficient macrophages compared with the inhibition in wild-type macrophages. A derivative of the minimal structural unit of peptidoglycan (6-O-stearoyl-muramyl dipeptide) recognized by nucleotide-binding oligomerization domain 2 (NOD2) could also suppress L. casei-induced IL-12 production. These findings demonstrate that easily digestible bacteria and peptidoglycan suppress IL-12 production through pattern recognition receptors such as TLR2 and NOD2. IL-12 production in the gut may be negatively regulated by the simultaneous inhibitory actions of various resident bacteria that are susceptible to intracellular digestion.
我们之前的研究表明，具有抵抗细胞内消化的刚性细胞壁的乳酸菌菌株可以刺激巨噬细胞诱导大量白细胞介素-12（IL-12）的产生。在这项研究中，我们研究了乳杆菌和细菌细胞壁成分对具有刚性细胞壁的干酪乳杆菌诱导的巨噬细胞产生 IL-12 的影响。容易消化的乳杆菌，如约翰逊乳杆菌和植物乳杆菌，或其完整的细胞壁（ICW），弱或非常弱地诱导巨噬细胞产生 IL-12，并且抑制干酪乳杆菌诱导的 IL-12 产生。虽然干酪乳杆菌的 ICW 抵抗细胞内消化并且不抑制干酪乳杆菌诱导的 IL-12 产生，但它的多糖耗尽的 ICW，即完整的肽聚糖，对细胞内消化敏感并且抑制干酪乳杆菌诱导的 IL-12 产生。此外，约翰逊乳杆菌、植物乳杆菌和金黄色葡萄球菌的肽聚糖也抑制干酪乳杆菌诱导的 IL-12 产生。来自乳杆菌的肽聚糖抑制干酪乳杆菌诱导的 IL-12p40 的表达，但不抑制 IL-12p35 mRNA 的表达。与野生型巨噬细胞相比，在 Toll 样受体 2（TLR2）缺陷型巨噬细胞中，肽聚糖对 IL-12 产生的抑制作用减轻。肽聚糖的最小结构单元（6-O-硬脂酰-胞壁酰二肽）的衍生物（NOD2）识别的核苷酸结合寡聚化结构域 2（NOD2）也可以抑制干酪乳杆菌诱导的 IL-12 产生。这些发现表明，容易消化的细菌和肽聚糖通过 TLR2 和 NOD2 等模式识别受体抑制 IL-12 的产生。肠道中的 IL-12 产生可能受到各种易受细胞内消化的常驻细菌的同时抑制作用的负调控。
