Choi Ji-Ae, Cho Soo-Na, Lee Junghwan, Son Sang-Hun, Nguyen Doan Tam, Lee Seong-Ahn, Song Chang-Hwa
Department of Microbiology, Department of Medical Science, College of Medicine, Chungnam National University, 266 Munhwa-ro, Jung-gu, 35015, Daejeon, South Korea.
Department of Medical Science, College of Medicine, Chungnam National University, 266 Munhwa-ro, Jung-gu, Daejeon, 35015, South Korea.
Cell Biosci. 2021 Sep 25;11(1):175. doi: 10.1186/s13578-021-00686-2.
Iron has important roles as an essential nutrient for all life forms and as an effector of the host defense mechanism against pathogenic infection. Lipocalin 2 (LCN2), an innate immune protein, plays a crucial role in iron transport and inflammation. In the present study, we examined the role of LCN2 in immune cells during Mycobacterium tuberculosis (Mtb) infection.
We found that infection with Mtb H37Ra induced LCN2 production in bone marrow-derived dendritic cells (BMDCs). Notably, expression of MHC class I molecules was significantly reduced in LCN2 BMDCs during Mtb infection. The reduced expression of MHC class I molecules was associated with the formation of a peptide loading complex through LCN2-mediated reactive oxygen species production. The reduced expression of MHC class I molecules affected CD8 T-cell proliferation in LCN2 mice infected with Mtb. The difference in the population of CD8 effector T cells might affect the survival of intracellular Mtb. We also found a reduction of the inflammation response, including serum inflammatory cytokines and lung inflammation in LCN2 mice, compared with wild-type mice, during Mtb infection.
These data suggest that LCN2-mediated reactive oxygen species affects expression of MHC class I molecules in BMDCs, leading to lower levels of CD8 effector T-cell proliferation during mycobacterial infection.
铁作为所有生命形式必需的营养素以及宿主抵御病原体感染的防御机制的效应物，具有重要作用。脂质运载蛋白2（LCN2）是一种天然免疫蛋白，在铁运输和炎症中起关键作用。在本研究中，我们研究了LCN2在结核分枝杆菌（Mtb）感染期间免疫细胞中的作用。
我们发现用Mtb H37Ra感染可诱导骨髓来源的树突状细胞（BMDCs）产生LCN2。值得注意的是，在Mtb感染期间，LCN2 BMDCs中MHC I类分子的表达显著降低。MHC I类分子表达的降低与通过LCN2介导的活性氧产生形成肽负载复合物有关。MHC I类分子表达的降低影响了感染Mtb的LCN2小鼠中CD8 T细胞的增殖。CD8效应T细胞群体的差异可能影响细胞内Mtb的存活。我们还发现，与野生型小鼠相比，在Mtb感染期间，LCN2小鼠的炎症反应降低，包括血清炎症细胞因子和肺部炎症。
这些数据表明，LCN2介导的活性氧影响BMDCs中MHC I类分子的表达，导致分枝杆菌感染期间CD8效应T细胞增殖水平降低。
