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LNCGM1082-mediated NLRC4 activation drives resistance to bacterial infection

Cellular & Molecular Immunology volume 20, pages 475–488 (2023)Cite this article

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Abstract

The activation of NLRC4 is a major host response against intracellular bacteria infection. However, NLRC4 activation after a host senses diverse stimuli is difficult to understand. Here, we found that the lncRNA LNCGM1082 plays a critical role in the activation of NLRC4. LNCGM1082 in macrophages affects the maturation of interleukin (IL)-1β and pyroptotic cell death only after exposure to an NLRC4 ligand. Similar to NLRC4−/− mice, LNCGM1082−/− mice were highly sensitive to Salmonella Typhimurium (S. T) infection. LNCGM1082 deficiency in mouse or human macrophages inhibited IL-1β maturation and pyroptosis. Mechanistically, LNCGM1082 induced the binding of PKCδ with NLRC4 in both mice and humans. In contrast, NLRC4 did not bind PKCδ in LNCGM1082−/− macrophages. The activity of the lncRNA LNCGM1082 induced by S. T may be mediated through TLR5 in the macrophages of both mice and humans. In summary, our data indicate that TLR5-mediated LNCGM1082 activity can promote the binding of PKCδ with NLRC4 to activate NLRC4 and induce resistance to bacterial infection.

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Data availability

Data from the microarray are available through the GEO database (Supplementary Fig. 3: Accession Number: GSE221313; Supplementary Fig. 9A: Accession Number: GSE173399; and Supplementary Fig. 14A, Accession Number: GSE173398).

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Acknowledgements

This research was supported by NSFC grants (grant numbers 81901677, 82271779, 91842302, 81970457, and 91629102); The Tianjin Science and Technology Commission (grant number, 18JCZDJC35300); A Ministry of Science and Technology (grant number, 2016YFC1303604); The State Key Laboratory of Medicinal Chemical Biology and the Fundamental Research Funds for the Central University, Nankai university (63191724).

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Authors and Affiliations

  1. Department of Immunology, Nankai University School of Medicine and Translational Medicine Institute, Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin, 300071, China

    Yunhuan Gao, Yazheng Yang, Jianmei Wei, Jianmei Yue, Ya Wang, Qianjing Zhang, Mengli Jin, Rong Wang, Xiaorong Yang, Yuan Zhang & Rongcun Yang

  2. State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China

    Yunhuan Gao & Rongcun Yang

  3. College of Life Science, Nankai University, Tianjin, 300121, China

    Junqi Zhang & Xinqi Liu

  4. China National Center for Bioinformation & Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China

    Lin Liu

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Contributions

RY designed the research and wrote the paper; YG conducted in vivo and in vitro experiments for identifying mechanisms of action; YY and QZ conducted most of the in vivo experiments and immunoassays; JW, JY, YW, MJ, RW, and XY performed some of the in vitro experiments; JZ, XL offered assistance for the ITC analyses, and YZ offered assistance for the animal experiments. All authors read and approved the final manuscript.

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Correspondence to Rongcun Yang.

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Gao, Y., Yang, Y., Wei, J. et al. LNCGM1082-mediated NLRC4 activation drives resistance to bacterial infection. Cell Mol Immunol 20, 475–488 (2023). https://doi.org/10.1038/s41423-023-00995-1

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