The role of innate immune responses in the outcome of interspecies competition for colonization of mucosal surfaces.
The role of innate immune responses in the outcome of interspecies competition for colonization of mucosal surfaces.
复制标题
DOI：
10.1371/journal.ppat.0010001
复制
发表时间：
2005-09
期刊：
影响因子：
6.7
通讯作者：
Weiser JN
中科院分区：
文献类型：
--
作者：
Lysenko ES;Ratner AJ;Nelson AL;Weiser JN
由于粘膜表面可能同时被多个物种定殖，因此生物体的成功可能取决于其与其生态位共存者竞争的能力。为了探讨宿主因素对多种微生物竞争的影响，使用小鼠模型来研究流感嗜血杆菌和肺炎链球菌定植的启动。这两种细菌在鼻咽部占据相似的微环境，当单独给予时，它们在定植期间持续存在。然而，共定植导致肺炎链球菌从上呼吸道快速清除，这与中性粒细胞招募到鼻旁空间的增加有关。中性粒细胞样细胞或补体的全身耗竭足以消除这种竞争效应，表明清除可能是由于增强的调理吞噬杀伤作用。使用诱导的中性粒细胞样细胞进行体外杀伤试验，测试了调理吞噬细胞活性的调节导致宿主介导的竞争的假设。流感嗜血杆菌（但不是肺炎链球菌）的成分刺激补体依赖性吞噬细胞杀死肺炎链球菌。因此，通过选择性微生物模式识别来招募和激活中性粒细胞可能是流感嗜血杆菌诱导的肺炎链球菌清除的基础。这项研究证明了先天免疫反应如何介导物种之间的竞争性相互作用并决定定植菌群的组成。细菌感染通常始于在粘膜表面定殖和增殖的微生物。这些微环境可能被多种微生物物种占据，这表明成功的殖民者以其战胜竞争对手的能力而著称。这项研究检查了两种定植并感染人类上呼吸道的细菌之间的相互作用。在小鼠模型中，单独测试时，流感嗜血杆菌和肺炎链球菌菌株都能有效定植于鼻粘膜。相反，在联合接种后，流感嗜血杆菌迅速且完全地战胜了肺炎链球菌。这种竞争效应取决于宿主以特定类型的白细胞（中性粒细胞）形式产生的局部反应，其作用是吞噬并杀死已被与微生物表面结合的蛋白质（补体）标记的微生物。这项研究的结果表明，识别一个物种的微生物产物可能会激活炎症反应，从而促进另一种竞争物种的清除。这项研究还表明，旨在减少单一病原体存在的抗生素或疫苗等操作可能会无意中改变复杂微生物群落的竞争性相互作用。
Since mucosal surfaces may be simultaneously colonized by multiple species, the success of an organism may be determined by its ability to compete with co-inhabitants of its niche. To explore the contribution of host factors to polymicrobial competition, a murine model was used to study the initiation of colonization by Haemophilus influenzae and Streptococcus pneumoniae. Both bacterial species, which occupy a similar microenvironment within the nasopharynx, persisted during colonization when given individually. Co-colonization, however, resulted in rapid clearance of S. pneumoniae from the upper respiratory tract, associated with increased recruitment of neutrophils into paranasal spaces. Systemic depletion of either neutrophil-like cells or complement was sufficient to eliminate this competitive effect, indicating that clearance was likely due to enhanced opsonophagocytic killing. The hypothesis that modulation of opsonophagocytic activity was responsible for host-mediated competition was tested using in vitro killing assays with elicited neutrophil-like cells. Components of H. influenzae (but not S. pneumoniae) stimulated complement-dependent phagocytic killing of S. pneumoniae. Thus, the recruitment and activation of neutrophils through selective microbial pattern recognition may underlie the H. influenzae–induced clearance of S. pneumoniae. This study demonstrates how innate immune responses may mediate competitive interactions between species and dictate the composition of the colonizing flora. Bacterial infection commonly begins with organisms that colonize and proliferate on mucosal surfaces. These microenvironments may be occupied by multiple microbial species, suggesting that successful colonizers are distinguished by their capacity to prevail over their competitors. This study examines interactions between two bacterial species that both colonize and infect the human upper respiratory tract. In a mouse model, strains of both Haemophilus influenzae and Streptococcus pneumoniae efficiently colonize the nasal mucosa when tested individually. In contrast, following co-inoculation, H. influenzae rapidly and completely outcompetes S. pneumoniae. This competitive effect is dependent on the local responses from the host in the form of a specific type of white blood cell (neutrophil) that acts to engulf and kill microorganisms that have been labeled by proteins that bind to microbial surfaces (complement). The results of this study show that recognition of microbial products from one species may activate inflammatory responses that promote the clearance of another competing species. This study also demonstrates how manipulations such as antibiotics or vaccines, which are meant to diminish the presence of a single pathogen, may inadvertently alter the competitive interactions of complex microbial communities.