Unknown

Dataset Information

0

IL-12+IL-18 Cosignaling in Human Macrophages and Lung Epithelial Cells Activates Cathelicidin and Autophagy, Inhibiting Intracellular Mycobacterial Growth.


ABSTRACT: The ability of Mycobacterium tuberculosis to block host antimicrobial responses in infected cells provides a key mechanism for disease pathogenesis. The immune system has evolved to overcome this blockade to restrict the infection, but it is not clear whether two key innate cytokines (IL-12/IL-18) involved in host defense can enhance antimycobacterial mechanisms. In this study, we demonstrated that the combination of IL-12 and IL-18 triggered an antimicrobial response against mycobacteria in infected macrophages (THP-1 and human primary monocyte-derived macrophages) and pulmonary epithelial A549 cells. The inhibition of intracellular bacterial growth required p38-MAPK and STAT4 pathways, the vitamin D receptor, the vitamin D receptor-derived antimicrobial peptide cathelicidin, and autophagy, but not caspase-mediated apoptosis. Finally, the ability of IL-12+IL-18 to activate an innate antimicrobial response in human primary macrophages was dependent on the autonomous production of IFN-? and the CAMP/autophagy pathway. Together, these data suggest that IL-12+IL-18 cosignaling can trigger the antimicrobial protein cathelicidin and autophagy, resulting in inhibition of intracellular mycobacteria in macrophages and lung epithelial cells.

SUBMITTER: Yang R 

PROVIDER: S-EPMC5860987 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications

IL-12+IL-18 Cosignaling in Human Macrophages and Lung Epithelial Cells Activates Cathelicidin and Autophagy, Inhibiting Intracellular Mycobacterial Growth.

Yang Rui R   Yang Enzhuo E   Shen Ling L   Modlin Robert L RL   Shen Hongbo H   Chen Zheng W ZW  

Journal of immunology (Baltimore, Md. : 1950) 20180216 7


The ability of <i>Mycobacterium tuberculosis</i> to block host antimicrobial responses in infected cells provides a key mechanism for disease pathogenesis. The immune system has evolved to overcome this blockade to restrict the infection, but it is not clear whether two key innate cytokines (IL-12/IL-18) involved in host defense can enhance antimycobacterial mechanisms. In this study, we demonstrated that the combination of IL-12 and IL-18 triggered an antimicrobial response against mycobacteria  ...[more]

Similar Datasets

| S-EPMC6497761 | biostudies-literature
| S-EPMC8889352 | biostudies-literature
| S-EPMC4588696 | biostudies-literature
| S-EPMC5442641 | biostudies-literature
| S-EPMC4297737 | biostudies-literature
| S-EPMC6145905 | biostudies-literature
| S-EPMC1895416 | biostudies-literature
| S-EPMC7608829 | biostudies-literature
| S-EPMC115087 | biostudies-literature
2022-02-02 | GSE166268 | GEO