Lipocalin 2 regulates expression of MHC class I molecules in Mycobacterium tuberculosis-infected dendritic cells via ROS production

Background 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. Results 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. Conclusions 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.

Automated summary

This study elucidates the role of LCN2 in regulating the expression of MHC class I molecules in immune cells during Mtb infection, subsequently impacting CD8(+) effector T-cell proliferation. LCN2(-/-) mice exhibited lower levels of inflammatory response during Mtb infection.