Gasdermin D‐independent release of interleukin‐1β by living macrophages in response to mycoplasmal lipoproteins and lipopeptides
- 26 June 2020
- journal article
- research article
- Published by Wiley in Immunology
- Vol. 161 (2), 114-122
- https://doi.org/10.1111/imm.13230
Abstract
Interleukin‐1b (IL‐1b) plays pivotal roles in controlling bacterial infections and is produced after the processing of pro‐IL‐1b 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‐1b. Living cells can also release IL‐1b 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‐1b release from mouse bone marrow‐derived macrophages (BMMs) without inducing cell death. The levels of IL‐1b 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‐1b 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‐1b was unaffected by GSDMD deficiency. Meanwhile, punicalagin, a membrane‐stabilizing agent, drastically downregulated the release of IL‐1b in response to FSL‐1. These results suggest that mycoplasmal lipoprotein/lipopeptide‐induced IL‐1b release by living macrophages is not mediated via GSDMD but rather through changes in membrane permeability.Keywords
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