TLR4 and TNFR1 signalling promotes potent proinflammatory signal transduction events, thus, are often hijacked by pathogenic microorganisms. We recently reported that myeloid cells retaliate Yersinia blockade of TAK1/IKK signalling by triggering RIPK1-dependent caspase-8 activation that promotes downstream GSDMD and GSDME-mediated pyroptosis in macrophages and neutrophils respectively. However, the upstream signalling events for RIPK1 activation in these cells are not well defined. Here, we demonstrate that unlike in macrophages, RIPK1-driven pyroptosis and cytokine priming in neutrophils are driven through TNFR1 signalling, while TLR4-TRIF signalling is dispensable. Furthermore, we demonstrate that activation of RIPK1-dependent pyroptosis in neutrophils during Yersinia infection requires IFN-γ priming, which serves to induce surface TNFR1 expression and amplify soluble TNF secretion. In contrast, macrophages utilise both TNFR1 and TLR4-TRIF signalling to trigger cell death, but only require TRIF but not autocrine TNFR1 for cytokine production. Together, these data highlight the emerging theme of cell type-specific regulation in cell death and immune signalling in myeloid cells.

TLR4 和 TNFR1 信号传导促进有效的促炎信号转导事件，因此经常被病原微生物劫持。我们最近报道，骨髓细胞通过触发 RIPK1 依赖性 caspase-8 激活来报复耶尔森菌对 TAK1/IKK 信号传导的阻断，从而分别促进下游 GSDMD 和 GSDME 介导的巨噬细胞和中性粒细胞焦亡。然而，这些细胞中 RIPK1 激活的上游信号事件尚未明确定义。在这里，我们证明，与巨噬细胞不同，中性粒细胞中 RIPK1 驱动的细胞焦亡和细胞因子引发是通过 TNFR1 信号传导驱动的，而 TLR4-TRIF 信号传导是可有可无的。此外，我们证明在耶尔森菌感染期间中性粒细胞中 RIPK1 依赖性细胞焦亡的激活需要 IFN-γ 启动，从而诱导表面 TNFR1 表达并放大可溶性 TNF 分泌。相比之下，巨噬细胞利用 TNFR1 和 TLR4-TRIF 信号传导来触发细胞死亡，但只需要 TRIF 而不需要自分泌 TNFR1 来产生细胞因子。总之，这些数据突出了骨髓细胞中细胞死亡和免疫信号传导中细胞类型特异性调节的新兴主题。