“孤立淋巴滤泡”（ILFs）是小肠壁中专门的淋巴组织区域，在那里它们参与保护宿主不受入侵病原体的侵害。对ILFs的组成及它们的形成所需因子所做的一项新的研究发现，它们是由来自革兰氏阴性细菌的肽聚糖的存在被上皮细胞中的NOD1先天受体识别出而在小鼠小肠中诱导产生的。ILFs的组成从由只有几个B细胞构成的细胞团到组织有序的淋巴结都有。一旦形成，ILFs便会对细菌群落的构成实施控制。哺乳动物中这一由微生物诱导的组织形成方式的罕见事例说明，细菌与宿主之间的一种建设性互动何以能够帮助实现高效消化和保护宿主不受小肠病原体侵害。

Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis

Djahida Bouskra 1 , Christophe Brézillon 2 , Marion Bérard 3 , Catherine Werts 4 , 6 , Rosa Varona 5 , Ivo Gomperts Boneca 4 , 6 & Gérard Eberl 1

1. Institut Pasteur, Laboratory of Lymphoid Tissue Development, CNRS, URA1961,
2. Institut Pasteur, Laboratoire des Bactéries Pathogènes Entériques,
3. Institut Pasteur, Animalerie Centrale
4. Institut Pasteur, Group of Biology and Genetics of the Bacterial Cell Wall, 25 rue du Dr Roux, Paris 75724, France
5. Department of Immunology and Oncology, Centro Nacional de Biotecnologia/CSIC, UAM Campus Cantoblanco, Madrid 28049, Spain
6. INSERM, Group AVENIR, Paris 75015, France

Intestinal homeostasis is critical for efficient energy extraction from food and protection from pathogens. Its disruption can lead to an array of severe illnesses with major impacts on public health, such as inflammatory bowel disease characterized by self-destructive intestinal immunity. However, the mechanisms regulating the equilibrium between the large bacterial flora and the immune system remain unclear. Intestinal lymphoid tissues generate flora-reactive IgA-producing B cells, and include Peyer’s patches and mesenteric lymph nodes, as well as numerous isolated lymphoid follicles (ILFs) . Here we show that peptidoglycan from Gram-negative bacteria is necessary and sufficient to induce the genesis of ILFs in mice through recognition by the NOD1 (nucleotide-binding oligomerization domain containing 1) innate receptor in epithelial cells, and β-defensin 3- and CCL20-mediated signalling through the chemokine receptor CCR6. Maturation of ILFs into large B-cell clusters requires subsequent detection of bacteria by toll-like receptors. In the absence of ILFs, the composition of the intestinal bacterial community is profoundly altered. Our results demonstrate that intestinal bacterial commensals and the immune system communicate through an innate detection system to generate adaptive lymphoid tissues and maintain intestinal homeostasis.

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