Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610, USA.
J Exp Med. 2011 Aug 1;208(8):1673-82. doi: 10.1084/jem.20101715. Epub 2011 Jul 11.
Microbes activate pattern recognition receptors to initiate adaptive immunity. T cells affect early innate inflammatory responses to viral infection, but both activation and suppression have been demonstrated. We identify a novel role for B cells in the early innate immune response during bacterial sepsis. We demonstrate that Rag1(-/-) mice display deficient early inflammatory responses and reduced survival during sepsis. Interestingly, B cell-deficient or anti-CD20 B cell-depleted mice, but not α/β T cell-deficient mice, display decreased inflammatory cytokine and chemokine production and reduced survival after sepsis. Both treatment of B cell-deficient mice with serum from wild-type (WT) mice and repletion of Rag1(-/-) mice with B cells improves sepsis survival, suggesting antibody-independent and antibody-dependent roles for B cells in the outcome to sepsis. During sepsis, marginal zone and follicular B cells are activated through type I interferon (IFN-I) receptor (IFN-α/β receptor [IFNAR]), and repleting Rag1(-/-) mice with WT, but not IFNAR(-/-), B cells improves IFN-I-dependent and -independent early cytokine responses. Repleting B cell-deficient mice with the IFN-I-dependent chemokine, CXCL10 was also sufficient to improve sepsis survival. This study identifies a novel role for IFN-I-activated B cells in protective early innate immune responses during bacterial sepsis.
微生物激活模式识别受体以启动适应性免疫。T 细胞影响病毒感染的早期固有炎症反应，但已证明其具有激活和抑制作用。我们在细菌性败血症的早期固有免疫反应中发现了 B 细胞的新作用。我们证明 Rag1(-/-) 小鼠在败血症期间表现出炎症反应不足和存活率降低。有趣的是，B 细胞缺陷或抗 CD20 B 细胞耗竭小鼠，而不是 α/β T 细胞缺陷小鼠，在败血症后表现出炎症细胞因子和趋化因子产生减少和存活率降低。用来自野生型 (WT) 小鼠的血清治疗 B 细胞缺陷小鼠和用 B 细胞补充 Rag1(-/-) 小鼠均可改善败血症的存活率，这表明 B 细胞在败血症结局中具有抗体依赖和非依赖的作用。在败血症期间，边缘区和滤泡 B 细胞通过 I 型干扰素 (IFN-I) 受体 (IFN-α/β 受体 [IFNAR]) 被激活，用 WT 而不是 IFNAR(-/-) B 细胞补充 Rag1(-/-) 小鼠可改善 IFN-I 依赖和非依赖的早期细胞因子反应。用 IFN-I 依赖性趋化因子 CXCL10 补充 B 细胞缺陷小鼠也足以提高败血症的存活率。这项研究确定了 IFN-I 激活的 B 细胞在细菌性败血症期间保护性早期固有免疫反应中的新作用。
