Lung epithelium as a sentinel and effector system in pneumonia molecular mechanisms of pathogen recognition and signal transduction

被引:120
作者
Hippenstiel, Stefan [1 ]
Opitz, Bastian [1 ]
Schmeck, Bernd [1 ]
Suttorp, Norbert [1 ]
机构
[1] Univ Med Berlin, Charite, Dept Internal Med Infect Dis & Resp Med, D-13353 Berlin, Germany
来源
RESPIRATORY RESEARCH | 2006年 / 7卷 / 1期
关键词
D O I
10.1186/1465-9921-7-97
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Pneumonia, a common disease caused by a great diversity of infectious agents is responsible for enormous morbidity and mortality worldwide. The bronchial and lung epithelium comprises a large surface between host and environment and is attacked as a primary target during lung infection. Besides acting as a mechanical barrier, recent evidence suggests that the lung epithelium functions as an important sentinel system against pathogens. Equipped with transmembranous and cytosolic pathogen-sensing pattern recognition receptors the epithelium detects invading pathogens. A complex signalling results in epithelial cell activation, which essentially participates in initiation and orchestration of the subsequent innate and adaptive immune response. In this review we summarize recent progress in research focussing on molecular mechanisms of pathogen detection, host cell signal transduction, and subsequent activation of lung epithelial cells by pathogens and their virulence factors and point to open questions. The analysis of lung epithelial function in the host response in pneumonia may pave the way to the development of innovative highly needed therapeutics in pneumonia in addition to antibiotics.
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页数:17
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共 257 条
[1]  
Aarbiou J, 2002, J LEUKOCYTE BIOL, V72, P167
[2]   TLR signaling in the gut in health and disease [J].
Abreu, MT ;
Fukata, M ;
Arditi, M .
JOURNAL OF IMMUNOLOGY, 2005, 174 (08) :4453-4460
[3]   Pseudomonas aeruginosa flagella activate airway epithelial cells through asialoGM1 and toll-like receptor 2 as well as toll-like receptor 5 [J].
Adamo, R ;
Sokol, S ;
Soong, G ;
Gomez, MI ;
Prince, A .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2004, 30 (05) :627-634
[4]   Toll-like receptor signalling [J].
Akira, S ;
Takeda, K .
NATURE REVIEWS IMMUNOLOGY, 2004, 4 (07) :499-511
[5]   Adenovirus type 7 induces interleukin-8 production via activation of extracellular regulated kinase 1/2 [J].
Alcorn, MJ ;
Booth, JL ;
Coggeshall, KM ;
Metcalf, JP .
JOURNAL OF VIROLOGY, 2001, 75 (14) :6450-6459
[6]   Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3 [J].
Alexopoulou, L ;
Holt, AC ;
Medzhitov, R ;
Flavell, RA .
NATURE, 2001, 413 (6857) :732-738
[7]   Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2 [J].
Aliprantis, AO ;
Yang, RB ;
Mark, MR ;
Suggett, S ;
Devaux, B ;
Radolf, JD ;
Klimpel, GR ;
Godowski, P ;
Zychlinsky, A .
SCIENCE, 1999, 285 (5428) :736-739
[8]   The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-β promoter [J].
Andrejeva, J ;
Childs, KS ;
Young, DF ;
Carlos, TS ;
Stock, N ;
Goodbourn, S ;
Randall, RE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (49) :17264-17269
[9]   Etiology of community-acquired pneumonia [J].
Apisarnthanarak, A ;
Mundy, LM .
CLINICS IN CHEST MEDICINE, 2005, 26 (01) :47-+
[10]   TLR4 mutations are associated with endotoxin hyporesponsiveness in humans [J].
Arbour, NC ;
Lorenz, E ;
Schutte, BC ;
Zabner, J ;
Kline, JN ;
Jones, M ;
Frees, K ;
Watt, JL ;
Schwartz, DA .
NATURE GENETICS, 2000, 25 (02) :187-+