THE ENDOGENOUS BACTERIA ALTER GUT EPITHELIAL APOPTOSIS AND DECREASE MORTALITY FOLLOWING PSEUDOMONAS AERUGINOSA PNEUMONIA

被引:50
作者
Fox, Amy C. [1 ]
McConnell, Kevin W. [2 ,3 ,4 ]
Yoseph, Benyam P. [2 ,3 ,4 ]
Breed, Elise [2 ,3 ,4 ]
Liang, Zhe [2 ,3 ,4 ]
Clark, Andrew T. [1 ]
O'Donnell, David [5 ]
Zee-Cheng, Brendan [1 ]
Jung, Enjae [1 ]
Dominguez, Jessica A. [1 ]
Dunne, W. Michael [6 ]
Burd, Eileen M. [4 ,7 ]
Coopersmith, Craig M. [2 ,3 ,4 ]
机构
[1] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA
[2] Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA
[3] Emory Univ, Sch Med, Emory Ctr Crit Care, Atlanta, GA USA
[4] Emory Healthcare, Atlanta, GA USA
[5] Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO USA
[6] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA
[7] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA
来源
SHOCK | 2012年 / 38卷 / 05期
基金
美国国家卫生研究院;
关键词
Sepsis; pneumonia; apoptosis; germ-free; endogenous bacteria; commensal microflora; intestine; gut; VENTILATOR-ASSOCIATED PNEUMONIA; BARRIER FUNCTION; GERM-FREE; HEMORRHAGIC-SHOCK; CRITICAL ILLNESS; DIGESTIVE-TRACT; SURVIVAL; DECONTAMINATION; TRANSLOCATION; LYMPHOCYTES;
D O I
10.1097/SHK.0b013e31826e47e8
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
The endogenous bacteria have been hypothesized to play a significant role in the pathophysiology of critical illness, although their role in sepsis is poorly understood. The purpose of this study was to determine how commensal bacteria alter the host response to sepsis. Conventional and germ-free (GF) C57Bl/6 mice were subjected to Pseudomonas aeruginosa pneumonia. All GF mice died within 2 days, whereas 44% of conventional mice survived for 7 days (P = 0.001). Diluting the dose of bacteria 10-fold in GF mice led to similar survival in GF and conventional mice. When animals with similar mortality were assayed for intestinal integrity, GF mice had lower levels of intestinal epithelial apoptosis but similar levels of proliferation and intestinal permeability. Germ-free mice had significantly lower levels of tumor necrosis factor and interleukin 1 beta in bronchoalveolar lavage fluid compared with conventional mice without changes in systemic cytokine production. Under conventional conditions, sepsis unmasks lymphocyte control of intestinal epithelial apoptosis, because sepsis induces a greater increase in gut apoptosis in Rag-1(-/-) mice than in wild-type mice. However, in a separate set of experiments, gut apoptosis was similar between septic GF Rag-1(-/-) mice and septic GF wild-type mice. These data demonstrate that the endogenous bacteria play a protective role in mediating mortality from pneumonia-induced sepsis, potentially mediated through altered intestinal apoptosis and the local proinflammatory response. In addition, sepsis-induced lymphocyte-dependent increases in gut epithelial apoptosis appear to be mediated by the endogenous bacteria.
引用
收藏
页码:508 / 514
页数:7
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