Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom;
Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom.
Proc Natl Acad Sci U S A. 2020 Aug 25;117(34):20717-20728. doi: 10.1073/pnas.2007472117. Epub 2020 Aug 11.
Mucosal-associated invariant T (MAIT) cells are innate T lymphocytes activated by bacteria that produce vitamin B2 metabolites. Mouse models of infection have demonstrated a role for MAIT cells in antimicrobial defense. However, proposed protective roles of MAIT cells in human infections remain unproven and clinical conditions associated with selective absence of MAIT cells have not been identified. We report that typhoidal and nontyphoidal strains activate MAIT cells. However, Typhimurium sequence type 313 (ST313) lineage 2 strains, which are responsible for the burden of multidrug-resistant nontyphoidal invasive disease in Africa, escape MAIT cell recognition through overexpression of This bacterial gene encodes the 4-dihydroxy-2-butanone-4-phosphate synthase enzyme of the riboflavin biosynthetic pathway. The MAIT cell-specific phenotype did not extend to other innate lymphocytes. We propose that overexpression is an evolved trait that facilitates evasion from immune recognition by MAIT cells and contributes to the invasive pathogenesis of Typhimurium ST313 lineage 2.
黏膜相关不变 T（MAIT）细胞是一种先天 T 淋巴细胞，可被产生维生素 B2 代谢物的细菌激活。感染的小鼠模型表明 MAIT 细胞在抗菌防御中发挥作用。然而，MAIT 细胞在人类感染中的保护作用仍未得到证实，也未确定与 MAIT 细胞选择性缺失相关的临床状况。我们报告称，伤寒和非伤寒菌株均可激活 MAIT 细胞。然而，引起非洲耐多药非伤寒性侵袭性疾病负担的鼠伤寒沙门氏菌血清型 313（ST313）谱系 2 菌株通过过度表达来逃避 MAIT 细胞的识别。该细菌基因编码核黄素生物合成途径的 4-二羟基-2-丁酮-4-磷酸合酶酶。MAIT 细胞特异性表型并未扩展到其他先天淋巴细胞。我们提出，过度表达是一种进化特征，可促进 MAIT 细胞逃避免疫识别，并有助于鼠伤寒沙门氏菌 ST313 谱系 2 的侵袭发病机制。
