Immune unresponsiveness to secondary heterologous bacterial infection after sepsis induction is TRAIL dependent.
Immune unresponsiveness to secondary heterologous bacterial infection after sepsis induction is TRAIL dependent.
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DOI：
10.4049/jimmunol.1101180
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发表时间：
2011-09-01
期刊：
影响因子：
--
通讯作者：
Griffith TS
中科院分区：
文献类型：
--
作者：
Gurung P;Rai D;Condotta SA;Babcock JC;Badovinac VP;Griffith TS
脓毒症是大多数ICU中死亡的主要原因，并且在脓毒症期间早期发展的过度炎症中存活的患者后来显示出严重受损的免疫力。在脓毒症期间，不仅存在淋巴细胞和骨髓细胞的凋亡，其耗尽免疫系统的这些关键细胞组分，而且剩余的免疫细胞也显示出功能降低。使用盲肠结扎和穿刺（CLP）模型，以诱导腹腔内多微生物腹膜炎，我们最近建立了一个链接，在脓毒症和诱导脓毒症诱导的迟发型超敏反应的抑制过程中产生的凋亡细胞。本研究扩展了这一早期工作，包括继发性异源细菌感染（OVA表达单核细胞增生李斯特菌; LM-OVA）后，脓毒症开始调查脓毒症诱导的改变，在控制这种继发性感染和相关的幼稚Ag特异性CD 8 T细胞反应。我们发现，CLP治疗的WT小鼠与假治疗的WT小鼠相比，控制LM-0 VA感染的能力降低，这是由抑制的T细胞应答引起的。相比之下，CLP处理的Trail−/−和Dr 5 −/−小鼠能够更好地控制继发性细菌感染，Ag特异性CD 8 T细胞应答与假处理小鼠中观察到的相似。重要的是，向CLP处理的WT小鼠施用阻断性抗TRAIL mAb能够恢复控制LM-0 VA感染的能力，并产生Ag特异性CD 8 T细胞应答，如在假处理的小鼠中所见。这些数据进一步暗示了脓毒症期间TRAIL依赖性免疫抑制，并表明TRAIL中和可能是恢复脓毒症患者细胞免疫的潜在治疗靶点。
Sepsis is the leading cause of death in most ICU’s, and patients who survive the hyper-inflammation that develops early during sepsis later display severely compromised immunity. Not only is there apoptosis of lymphoid and myeloid cells during sepsis that depletes these critical cellular components of the immune system, but the remaining immune cells also show decreased function. Using a cecal-ligation and puncture (CLP) model to induce intra-abdominal polymicrobial peritonitis, we recently established a link between the apoptotic cells generated during sepsis and induction of sepsis-induced suppression of delayed-type hypersensitivity. The present study extends this earlier work to include a secondary heterologous bacterial infection (OVA-expressing Listeria monocytogenes; LM-OVA) subsequent to sepsis initiation to investigate sepsis-induced alterations in the control of this secondary infection and the associated naïve Ag-specific CD8 T cell response. We found that CLP-treated WT mice had a reduced ability to control the LM-OVA infection, which was paralleled by suppressed T cell responses, versus sham-treated WT mice. In contrast, CLP-treated Trail−/− and Dr5−/− mice were better able to control the secondary bacterial infection and the Ag-specific CD8 T cell response was similar to that seen in sham-treated mice. Importantly, administration of a blocking anti-TRAIL mAb to CLP-treated WT mice was able to restore the ability to control the LM-OVA infection and generate Ag-specific CD8 T cell responses like those seen in sham-treated mice. These data further implicate TRAIL-dependent immune suppression during sepsis, and suggest TRAIL neutralization may be a potential therapeutic target to restore cellular immunity in septic patients.
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影响因子：
4.4
作者：
Ferguson, TA;Herndon, J;Green, DR
通讯作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.96.25.14541
发表时间：
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发表时间：
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影响因子：
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作者：
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影响因子：
4.4
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