PDF(Pubmed)
Abstract：
Mucosal-associated invariant T (MAIT) cells are restricted by MR1 and are known to protect against bacterial and viral infections. Our understanding of the role of MAIT cells in parasitic infections, such as visceral leishmaniasis (VL) caused by protozoan parasites of Leishmania donovani, is limited. This study showed that in response to L. infantum, human peripheral blood MAIT cells from children with leishmaniasis produced TNF and IFN-γ in an MR1-dependent manner. The overall frequency of MAIT cells was inversely correlated with alanine aminotransferase levels, a specific marker of liver damage strongly associated with severe hepatic involvement in VL. In addition, there was a positive correlation between total protein levels and the frequency of IL-17A+ CD8+ MAIT cells, whereby reduced total protein levels are a marker of liver and kidney damage. Furthermore, the frequencies of IFN-γ+ and IL-10+ MAIT cells were inversely correlated with hemoglobin levels, a marker of severe anemia. In asymptomatic individuals and VL patients after treatment, MAIT cells also produced IL-17A, a cytokine signature associated with resistance to visceral leishmaniasis, suggesting that MAIT cells play important role in protecting against VL. In summary, these results broaden our understanding of MAIT-cell immunity to include protection against parasitic infections, with implications for MAIT-cell-based therapeutics and vaccines. At last, this study paves the way for the investigation of putative MAIT cell antigens that could exist in the context of Leishmania infection.
摘要：
粘膜相关的不变T(MAIT)细胞受MR1限制,并且已知防止细菌和病毒感染。我们对MAIT细胞在寄生虫感染中的作用的理解，例如由利什曼原虫的原生动物寄生虫引起的内脏利什曼病（VL），是有限的。这项研究表明，在对L.infantum的反应中，来自利什曼病患儿的人外周血MAIT细胞以MR1依赖性方式产生TNF和IFN-γ。MAIT细胞的总体频率与丙氨酸转氨酶水平呈负相关，与VL严重肝脏受累密切相关的肝脏损害的特异性标志物。此外,总蛋白水平与IL-17A+CD8+MAIT细胞频率呈正相关,其中降低的总蛋白水平是肝和肾损害的标志。此外，IFN-γ+和IL-10+MAIT细胞的频率与血红蛋白水平呈负相关，严重贫血的标志.在无症状个体和治疗后的VL患者中，MAIT细胞还产生IL-17A，与内脏利什曼病抗性相关的细胞因子特征，提示MAIT细胞在保护VL中起重要作用。总之,这些结果扩大了我们对MAIT细胞免疫的理解，包括对寄生虫感染的保护，对MAIT细胞疗法和疫苗的影响。最后,这项研究为研究可能存在于利什曼原虫感染的假定MAIT细胞抗原铺平了道路。
