| First Author | Saeki A | Year | 2020 |
| Journal | Immunology | Volume | 161 |
| Issue | 2 | Pages | 114-122 |
| PubMed ID | 32592165 | Mgi Jnum | J:297562 |
| Mgi Id | MGI:6474026 | Doi | 10.1111/imm.13230 |
| Citation | Saeki A, et al. (2020) Gasdermin D-independent release of interleukin-1beta by living macrophages in response to mycoplasmal lipoproteins and lipopeptides. Immunology |
| abstractText | Interleukin-1beta (IL-1beta) plays pivotal roles in controlling bacterial infections and is produced after the processing of pro-IL-1beta by caspase-1, which is activated by the inflammasome. In addition, caspase-1 cleaves the cytosolic protein, gasdermin-D (GSDMD), whose N-terminal fragment subsequently forms a pore in the plasma membrane, leading to the pyroptic cell-death-mediated release of IL-1beta. Living cells can also release IL-1beta via GSDMD pores or other unconventional secretory pathways. However, the precise mechanisms are poorly defined. Here, we show that lipoproteins from Mycoplasma salivarium (MsLP) and Mycoplasma pneumoniae (MpLP) and an M. salivarium-derived lipopeptide (FSL-1), which are activators of the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome, induce IL-1beta release from mouse bone-marrow-derived macrophages (BMMs) without inducing cell death. The levels of IL-1beta release induced by MsLP, MpLP and FSL-1 were more than 100 times lower than those induced by the canonical NLRP3 activator nigericin. The IL-1beta release-inducing activities of MsLP, MpLP and FSL-1 were not attenuated in BMMs from GSDMD-deficient mice. Furthermore, both active caspase-1 and cleaved GSDMD were detected in response to transfection of FSL-1 into the cytosol of BMMs, but the release of IL-1beta was unaffected by GSDMD deficiency. Meanwhile, punicalagin, a membrane-stabilizing agent, drastically down-regulated the release of IL-1beta in response to FSL-1. These results suggest that mycoplasmal lipoprotein/lipopeptide-induced IL-1beta release by living macrophages is not mediated via GSDMD but rather through changes in membrane permeability. |
