Wolbachia limits pathogen infections through induction of host innate immune responses

BackgroundWolbachia has been reported to suppress a variety of pathogen infections in mosquitoes, but the mechanism is undefined. Two possibilities have been proposed. One is that Wolbachia activates host immune responses, and the other one is that Wolbachia competes with pathogens for limited nutrients.Methodology/Principal findingsIn this study, we compared host immune responses and the densities of two different strains of Wolbachia in naturally occurring parental and artificially created hybrid host genetic backgrounds. No significant difference in Wolbachia density was found between these hosts. We found that Wolbachia could activate host innate immune responses when the host genetic profile was different from that of its natural host. When these hosts were challenged with pathogenic bacteria, mosquitoes in new host-Wolbachia symbioses had a higher survival rate than in old host-Wolbachia symbioses.Conclusions/SignificanceThe presence of Wolbachia per se does not necessarily affect pathogen infections, suggesting that a competition for limited nutrients is not the main reason for Wolbachia-mediated pathogen suppression. Instead, host immune responses are responsible for it. The elucidation of an immunity nature of PI is important to guide future practice: Wolbachia may be genetically engineered to be more immunogenic, it is desired to search and isolate more strains of Wolbachia, and test more host-Wolbachia symbioses for future applications. Our results also suggest Wolbachia-based PI may be applied to naturally Wolbachia-infected mosquito populations, and extend to the control of a broader range of mosquito-borne diseases.

研究背景：已有研究表明，沃尔巴克氏体（Wolbachia）可抑制蚊子体内的多种病原体感染，但其具体作用机制尚未明确。目前已提出两种潜在假说：其一为沃尔巴克氏体可激活宿主免疫应答；其二为沃尔巴克氏体与病原体竞争有限的营养物质。
研究方法与主要结果：本研究针对天然亲本宿主与人工构建的杂交宿主遗传背景，对比分析了宿主免疫应答以及两种不同沃尔巴克氏体菌株的载量。结果显示，两类宿主的沃尔巴克氏体载量无显著差异。研究发现，当宿主遗传背景与其天然宿主存在差异时，沃尔巴克氏体可激活宿主先天免疫应答；当用致病菌攻毒宿主后，新型宿主-沃尔巴克氏体共生体系的蚊子存活率显著高于传统宿主-沃尔巴克氏体共生体系。
结论与意义：沃尔巴克氏体本身未必会直接影响病原体感染，这表明营养竞争并非沃尔巴克氏体介导病原体抑制的主要机制，宿主免疫应答才是其核心作用途径。阐明病原体抑制（Pathogen Inhibition，PI）的免疫机制对指导后续研究具有重要意义：可通过基因工程手段改造沃尔巴克氏体以增强其免疫原性，还应筛选并分离更多沃尔巴克氏体菌株，测试更多宿主-沃尔巴克氏体共生体系以拓展其应用场景。本研究结果同时表明，基于沃尔巴克氏体的病原体抑制策略可应用于天然携带沃尔巴克氏体的蚊子种群，进而为防控更多种类的蚊媒传染病提供新思路。