Riboflavin Metabolism Variation among Clinical Isolates of Streptococcus pneumoniae Results in Differential Activation of Mucosal-associated Invariant T Cells
Riboflavin Metabolism Variation among Clinical Isolates of Streptococcus pneumoniae Results in Differential Activation of Mucosal-associated Invariant T Cells
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DOI：
10.1165/rcmb.2017-0290oc
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发表时间：
2018-06-01
影响因子：
6.4
通讯作者：
Harriff, Melanie J.
中科院分区：
文献类型：
--
作者：
Hartmann, Nadine;McMurtrey, Curtis;Harriff, Melanie J.
肺炎链球菌是一种重要的细菌病原体，可引起一系列非侵袭性和侵袭性疾病。肺炎链球菌从鼻咽定植转变为致病病原体的能力变异的机制尚不清楚。粘膜相关不变 T (MAIT) 细胞普遍存在于气道等粘膜组织中，被认为在细菌病原体感染的早期反应中发挥着重要作用。 MAIT 细胞识别和遏制肺炎链球菌感染的能力尚不清楚。在本研究中，我们分析了 MAIT 细胞对肺炎链球菌血清型 19A（一种与侵袭性肺炎球菌疾病相关的血清型）临床分离株感染的反应。我们发现，尽管 MAIT 细胞能够对感染肺炎链球菌的人树突状细胞和气道上皮细胞做出反应，但对不同血清型 19A 分离株的反应程度是由核黄素生物合成途径表达的遗传差异决定的。 MAIT 细胞释放的细胞因子与小鼠攻击模型中体外和体内 MAIT 细胞响应和控制肺炎链球菌的能力差异相关。总之，这些结果首先证明，相同血清型的临床分离株之间的核黄素代谢存在遗传差异，其次，这些可能决定了 MAIT 细胞对肺炎链球菌感染的反应功能。当考虑 MAIT 细胞在肺炎球菌感染的早期反应中所发挥的作用以及确定是否会发生侵袭性疾病时，这些差异至关重要。
Streptococcus pneumoniae is an important bacterial pathogen that causes a range of noninvasive and invasive diseases. The mechanisms underlying variability in the ability of S. pneumoniae to transition from nasopharyngeal colonization to disease-causing pathogen are not well defined. Mucosal-associated invariant T (MAIT) cells are prevalent in mucosal tissues such as the airways and are believed to play an important role in the early response to infection with bacterial pathogens. The ability of MAIT cells to recognize and contain infection with S. pneumoniae is not known. In the present study, we analyzed MAIT-cell responses to infection with clinical isolates of S. pneumoniae serotype 19A, a serotype linked to invasive pneumococcal disease. We found that although MAIT cells were capable of responding to human dendritic and airway epithelial cells infected with S. pneumoniae, the magnitude of response to different serotype 19A isolates was determined by genetic differences in the expression of the riboflavin biosynthesis pathway. MAIT-cell release of cytokines correlated with differences in the ability of MAIT cells to respond to and control S. pneumoniae in vitro and in vivo in a mouse challenge model. Together, these results demonstrate first that there are genetic differences in riboflavin metabolism among clinical isolates of the same serotype and second that these likely determine MAIT-cell function in response to infection with S. pneumoniae. These differences are critical when considering the role that MAIT cells play in early responses to pneumococcal infection and determining whether invasive disease will develop.