PDF(Pubmed)
Abstract：
Tumor necrosis factor (TNF) is a pleiotropic inflammatory cytokine that mediates antimicrobial defense and granuloma formation in response to infection by numerous pathogens. We previously reported that Yersinia pseudotuberculosis colonizes the intestinal mucosa and induces the recruitment of neutrophils and inflammatory monocytes into organized immune structures termed pyogranulomas (PG) that control Yersinia infection. Inflammatory monocytes are essential for the control and clearance of Yersinia within intestinal PG, but how monocytes mediate Yersinia restriction is poorly understood. Here, we demonstrate that TNF signaling in monocytes is required for bacterial containment following enteric Yersinia infection. We further show that monocyte-intrinsic TNFR1 signaling drives the production of monocyte-derived interleukin-1 (IL-1), which signals through IL-1 receptors on non-hematopoietic cells to enable PG-mediated control of intestinal Yersinia infection. Altogether, our work reveals a monocyte-intrinsic TNF-IL-1 collaborative inflammatory circuit that restricts intestinal Yersinia infection.
摘要：
肿瘤坏死因子（TNF）是一种多效性炎性细胞因子，可介导抗微生物防御和肉芽肿形成，以应对多种病原体的感染。我们先前报道过假结核耶尔森氏菌定植于肠粘膜，并诱导嗜中性粒细胞和炎性单核细胞募集到控制耶尔森氏菌感染的称为脓性肉芽肿（PG）的有组织免疫结构中。炎性单核细胞对于控制和清除肠道PG内的耶尔森氏菌至关重要，但对单核细胞如何介导耶尔森氏菌限制的了解甚少。这里,我们证明，单核细胞中的TNF信号传导是肠道耶尔森氏菌感染后细菌遏制所必需的。我们进一步表明，单核细胞固有的TNFR1信号驱动单核细胞衍生的白细胞介素-1（IL-1）的产生，它通过非造血细胞上的IL-1受体发出信号，以使PG介导的肠耶尔森氏菌感染得到控制。总之,我们的工作揭示了单核细胞-内源性TNF-IL-1协同炎症回路,可限制肠道耶尔森氏菌感染.
