Chronic Alcohol Ingestion Delays T Cell Activation and Effector Function in Sepsis.
Chronic Alcohol Ingestion Delays T Cell Activation and Effector Function in Sepsis.
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DOI：
10.1371/journal.pone.0165886
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Ford ML
中科院分区：
文献类型：
--
作者：
Margoles LM;Mittal R;Klingensmith NJ;Lyons JD;Liang Z;Serbanescu MA;Wagener ME;Coopersmith CM;Ford ML
脓毒症是美国重症监护病房死亡的主要原因，并且已知慢性酒精使用与脓毒症的发生率较高、ICU停留时间较长以及脓毒症的死亡率较高相关。脓毒症和长期饮酒都与免疫缺陷有关，如淋巴细胞数量减少、先天免疫受损、迟发型超敏反应和感染易感性;然而，缺乏对这两种免疫失调状态之间相互作用或协同作用的特定途径的理解。因此，本研究旨在阐明慢性酒精暴露背景下脓毒症期间观察到的免疫失调的机制。使用慢性乙醇摄入，然后通过盲肠结扎和穿孔诱导脓毒症的小鼠模型，我们确定，虽然从酒精喂养的小鼠中分离的CD 4+和CD 8 + T细胞最终表达相同的细胞活化标志物（CD 44、CD 69和CD 43）和效应分子（IFN-γ、TNF）作为它们的水喂养对应物，但这些表型的获得总体上有所延迟。T细胞活化的这种早期滞后与酒精脓毒症中的CD 4+和CD 8 + T细胞区室中在稍后时间点显著降低的IL-2产生以及CD 8dim活化效应物的累积减少相关。综上所述，这些数据表明，延迟T细胞活化可能导致在慢性酒精摄入的设置中对脓毒症的免疫应答的质的差异。
Sepsis is the leading cause of death in intensive care units in the US, and it is known that chronic alcohol use is associated with higher incidence of sepsis, longer ICU stays, and higher mortality from sepsis. Both sepsis and chronic alcohol use are associated with immune deficits such as decreased lymphocyte numbers, impaired innate immunity, delayed-type hypersensitivity reactions, and susceptibility to infections; however, understanding of specific pathways of interaction or synergy between these two states of immune dysregulation is lacking. This study therefore sought to elucidate mechanisms underlying the immune dysregulation observed during sepsis in the setting of chronic alcohol exposure. Using a murine model of chronic ethanol ingestion followed by sepsis induction via cecal ligation and puncture, we determined that while CD4+ and CD8+ T cells isolated from alcohol fed mice eventually expressed the same cellular activation markers (CD44, CD69, and CD43) and effector molecules (IFN-γ, TNF) as their water fed counterparts, there was an overall delay in the acquisition of these phenotypes. This early lag in T cell activation was associated with significantly reduced IL-2 production at a later timepoint in both the CD4+ and CD8+ T cell compartments in alcohol sepsis, as well as with a reduced accumulation of CD8dim activated effectors. Taken together, these data suggest that delayed T cell activation may result in qualitative differences in the immune response to sepsis in the setting of chronic alcohol ingestion.
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影响因子：
3.7
作者：
Beus JM;Hashmi SS;Selvaraj SA;Duan D;Stempora LL;Monday SA;Cheeseman JA;Hamby KM;Speck SH;Larsen CP;Kirk AD;Kean LS
通讯作者：
Kean LS
DOI：
10.1038/nri3552
发表时间：
2013-12
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.8
作者：
MANJUNATH, N;CORREA, M;ARDMAN, B
通讯作者：
ARDMAN, B
影响因子：
37.8
作者：
Cruz-Adalia, Aranzazu;Jesus Jimenez-Borreguero, Luis;Martin, Pilar
通讯作者：
Martin, Pilar
影响因子：
5.3
作者：
de la Fuente, Hortensia;Cruz-Adalia, Aranzazu;Sanchez-Madrid, Francisco
通讯作者：
Sanchez-Madrid, Francisco