Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan.
J Immunol. 2010 Aug 15;185(4):2424-31. doi: 10.4049/jimmunol.1000625. Epub 2010 Jul 16.
Pathogenic bacteria mitigate host immunity to establish infections, but the mechanism of this bacterial action has not been fully elucidated. To search for cell wall components that modulate innate immune responses in host organisms, we examined Staphylococcus aureus mutants, which were deficient in components of the cell wall, for pathogenicity in Drosophila. A mutation of dltA, which is responsible for the D-alanylation of teichoic acids, brought about an increase in the survival rate of adult flies that had received a septic infection with the bacteria. The growth of dltA-deficient S. aureus in adult flies was less efficient than that of the parental strain. The level of mRNA of Toll pathway-dependent antimicrobial peptides was higher in flies infected with the dltA mutant than that observed after the infection with the parental strain. The defective phenotype associated with the mutation of dltA, reduced pathogenicity and growth, was not evident in flies lacking the Toll pathway. Finally, a fraction of peptidoglycan prepared from the dltA mutant induced the expression of mRNA of a Toll-dependent antimicrobial peptide in flies and was bound by peptidoglycan recognition protein-SA in vitro more effectively than that obtained from the parental strain, and this difference was lost after the removal of wall teichoic acid from peptidoglycan. Taken together, we conclude that D-alanylated wall teichoic acid of S. aureus mitigates a Toll-mediated humoral response in Drosophila interfering with the recognition of peptidoglycan by a pattern recognition receptor.
致病菌减轻宿主的免疫反应以建立感染，但这种细菌作用的机制尚未完全阐明。为了寻找调节宿主生物固有免疫反应的细胞壁成分，我们研究了金黄色葡萄球菌突变体，这些突变体缺乏细胞壁成分，以确定它们在果蝇中的致病性。负责磷壁酸 D-丙氨酸化的 dltA 突变导致接受细菌败血症感染的成年果蝇存活率增加。与亲本菌株相比，dltA 缺陷型金黄色葡萄球菌在成年果蝇中的生长效率较低。与亲本菌株感染相比，感染 dltA 突变体的果蝇中 Toll 途径依赖性抗菌肽的 mRNA 水平更高。与 Toll 途径缺失相关的缺陷表型，包括致病性降低和生长不良，在缺乏 Toll 途径的果蝇中并不明显。最后，从 dltA 突变体中制备的肽聚糖片段在果蝇中诱导 Toll 依赖性抗菌肽的 mRNA 表达，并比从亲本菌株获得的肽聚糖片段更有效地与肽聚糖识别蛋白-SA 结合，并且这种差异在从肽聚糖中去除壁磷壁酸后消失。综上所述，我们得出结论，金黄色葡萄球菌的 D-丙氨酸化壁磷壁酸减轻了果蝇中的 Toll 介导的体液反应，干扰了模式识别受体对肽聚糖的识别。
