The mammalian immune system is equipped with unconventional T cells that respond to microbial molecules such as glycolipids and small-molecule metabolites, which are invisible to conventional CD4 and CD8 T cells. Unconventional T cells include invariant natural killer T (iNKT) cells and mucosa-associated invariant T (MAIT) cells, which are involved in a wide range of infectious and non-infectious diseases, such as cancer and autoimmunity. In addition, their high conservation across mammals, their restriction by non-polymorphic antigen-presenting molecules, and their immediate and robust responses make these ‘innate’ T cells appealing targets for the development of one-size-fits-all immunotherapies. In this review, we discuss how iNKT and MAIT cells directly and indirectly detect the presence of and respond to pathogenic and commensal microbes. We also explore the current understanding of the bidirectional relationship between the microbiota and innate T cells, and how this crosstalk shapes the immune response in disease.

哺乳动物免疫系统配备了非常规 T 细胞，这些 T 细胞对糖脂和小分子代谢物等微生物分子有反应，而传统 CD4 和 CD8 T 细胞则看不到这些分子。非常规 T 细胞包括不变性自然杀伤 T (iNKT) 细胞和粘膜相关不变性 T (MAIT) 细胞，它们参与广泛的感染性和非感染性疾病，例如癌症和自身免疫。此外，它们在哺乳动物中的高度保守性、它们对非多态性抗原呈递分子的限制以及它们的即时和强大反应使这些“先天性”T 细胞成为开发通用免疫疗法的有吸引力的目标。在这篇综述中，我们讨论了 iNKT 和 MAIT 细胞如何直接和间接地检测致病微生物和共生微生物的存在并对其作出反应。