Vacca Maurizio, Böhme Julia, Zambetti Lia Paola, Khameneh Hanif Javanmard, Paleja Bhairav S, Laudisi Federica, Ho Adrian W S, Neo Kurt, Leong Keith Weng Kit, Marzuki Mardiana, Lee Bernett, Poidinger Michael, Santambrogio Laura, Tsenova Liana, Zolezzi Francesca, De Libero Gennaro, Singhal Amit, Mortellaro Alessandra
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Front Immunol. 2017 Nov 2;8:1462. doi: 10.3389/fimmu.2017.01462. eCollection 2017.
NLRP10 is a nucleotide-binding oligomerization domain-like receptor that functions as an intracellular pattern recognition receptor for microbial products. Here, we generated a mouse to delineate the role of NLRP10 in the host immune response and found that dendritic cells (DCs) elicited sub-optimal IFNγ production by antigen-specific CD4 T cells compared to wild-type (WT) DCs. In response to T-cell encounter, CD40 ligation or Toll-like receptor 9 stimulation, DCs produced low levels of IL-12, due to a substantial decrease in NF-κB activation. Defective IL-12 production was also evident and affected IFNγ production by CD4 T cells. Upon () infection, mice displayed diminished T helper 1-cell responses and increased bacterial growth compared to WT mice. These data indicate that NLRP10-mediated IL-12 production by DCs is critical for IFNγ induction in T cells and contributes to promote the host defense against .
NLRP10是一种核苷酸结合寡聚化结构域样受体,作为微生物产物的细胞内模式识别受体发挥作用。在此,我们构建了一种小鼠模型来阐明NLRP10在宿主免疫反应中的作用,发现与野生型(WT)树突状细胞(DC)相比,NLRP10缺陷型DC诱导抗原特异性CD4 T细胞产生的IFNγ水平次优。在与T细胞相遇、CD40连接或Toll样受体9刺激时,由于NF-κB激活大幅减少,NLRP10缺陷型DC产生的IL-12水平较低。IL-12产生缺陷也很明显,并影响CD4 T细胞产生IFNγ。在感染()后,与WT小鼠相比,NLRP10缺陷型小鼠的辅助性T1细胞反应减弱,细菌生长增加。这些数据表明,NLRP10介导的DC产生IL-12对于T细胞中IFNγ的诱导至关重要,并有助于促进宿主对()的防御。