Department of Medicine, Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Cell Host Microbe. 2011 Nov 17;10(5):437-50. doi: 10.1016/j.chom.2011.09.011.
iNKT cells are innate T lymphocytes recognizing endogenous and foreign lipid antigens presented in the MHC-like molecule CD1d. The semi-invariant iNKT cell TCR can detect certain bacterial and parasitic lipids and drive iNKT cell responses. How iNKT cells respond to fungi, however, is unknown. We found that CD1d-deficient mice, which lack iNKT cells, poorly control infection with the fungal pathogen Aspergillus fumigatus. Furthermore, A. fumigatus rapidly activates iNKT cells in vivo and in vitro in the presence of APCs. Surprisingly, despite a requirement for CD1d recognition, the antifungal iNKT cell response does not require fungal lipids. Instead, Dectin-1- and MyD88-mediated responses to β-1,3 glucans, major fungal cell-wall polysaccharides, trigger IL-12 production by APCs that drives self-reactive iNKT cells to secrete IFN-γ. Innate recognition of β-1,3 glucans also drives iNKT cell responses against Candida, Histoplasma, and Alternaria, suggesting that this mechanism may broadly define the basis for antifungal iNKT cell responses.
iNKT 细胞是先天 T 淋巴细胞，能够识别 MHC 样分子 CD1d 呈递的内源性和外源性脂质抗原。半不变的 iNKT 细胞 TCR 可以检测某些细菌和寄生虫脂质，并驱动 iNKT 细胞反应。然而，iNKT 细胞如何对真菌做出反应尚不清楚。我们发现，缺乏 iNKT 细胞的 CD1d 缺陷小鼠对真菌病原体烟曲霉的感染控制不佳。此外，在 APC 的存在下，烟曲霉在体内和体外迅速激活 iNKT 细胞。令人惊讶的是，尽管需要 CD1d 识别，但抗真菌 iNKT 细胞反应不需要真菌脂质。相反，Dectin-1 和 MyD88 介导的对β-1,3 葡聚糖的反应，主要是真菌细胞壁多糖，触发 APC 产生 IL-12，从而驱动自身反应性 iNKT 细胞分泌 IFN-γ。对β-1,3 葡聚糖的先天识别也驱动了 iNKT 细胞对念珠菌、组织胞浆菌和链格孢菌的反应，这表明该机制可能广泛定义了抗真菌 iNKT 细胞反应的基础。
