Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, California, USA.
Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA.
Infect Immun. 2018 Apr 23;86(5). doi: 10.1128/IAI.00878-17. Print 2018 May.
The epithelial layer of the gastrointestinal tract contains invaginations, called glands or crypts, which are colonized by symbiotic and pathogenic microorganisms and may function as designated niches for certain species. Factors that control gland colonization are poorly understood, but bacterial chemotaxis aids occupation of these sites. We report here that a cytoplasmic chemoreceptor, TlpD, is required for gland colonization in the stomach. mutants demonstrate gland colonization defects characterized by a reduction in the percentage of glands colonized but not in the number of bacteria per gland. Consistent with TlpD's reported role in reactive oxygen species (ROS) avoidance, mutants showed hallmarks of exposure to high ROS. To assess the role of host-generated ROS in TlpD-dependent gland colonization, we utilized mice that lack either the ability to generate epithelial hydrogen peroxide or immune cell superoxide. gland colonization defects were rescued to wild-type levels in both of these mutants. These results suggest that multiple types of innate immune-generated ROS production limit gland colonization and that bacteria have evolved specific mechanisms to sense and direct their motility in response to this signal and thus spread throughout tissue.
胃肠道的上皮层包含内陷，称为腺体或隐窝，这些内陷被共生和病原微生物定植，并且可能作为某些物种的指定生态位发挥作用。控制腺体定植的因素知之甚少，但细菌的趋化作用有助于占领这些部位。我们在这里报告，一种细胞质化学感受器 TlpD，是胃中腺体定植所必需的。ΔtlpD 突变体表现出腺体定植缺陷的特征，表现为定植的腺体百分比减少，但每个腺体中的细菌数量没有减少。与 TlpD 报道的在活性氧 (ROS) 避免中的作用一致，ΔtlpD 突变体表现出暴露于高 ROS 的特征。为了评估宿主产生的 ROS 在 TlpD 依赖性腺体定植中的作用，我们利用缺乏产生上皮过氧化氢或免疫细胞超氧化物能力的小鼠。在这两种突变体中，ΔtlpD 突变体的腺体定植缺陷均被挽救至野生型水平。这些结果表明，多种类型的固有免疫产生的 ROS 产生限制了腺体定植，并且细菌已经进化出特定的机制来感知和指导其运动以响应这种信号，从而在组织中扩散。
