Lipopolysaccharide sensing an important factor in the innate immune response to Gram-negative bacterial infections: benefits and hazards of LPS hypersensitivity.
In this review, we summarize our investigations concerning the differential importance of CD14 and LBP in toll-like receptor 4 (TLR4)/myeloid differentiation protein-2 (MD-2)-mediated signaling by smooth and rough-form lipopolysaccharide (LPS) chemotypes and include the results obtained in studies with murine and human TLR4-transgenic mice. Furthermore, we present more recent data on the mechanisms involved in the induction of LPS hypersensitivity by bacterial and viral infections and on the reactivity of the hypersensitive host to non-LPS microbial ligands and endogenous mediators. Finally, the effects of pre-existing hypersensitivity on the course and outcome of a super-infection with Salmonella typhimurium or Listeria monocytogenes are summarized.
Freudenberg
Marina A
MA
Max-Planck-Institute for Immunobiology, Stübeweg 51, D-79108 Freiburg, Germany. freudenberg@immunobio.mpg.de
Tchaptchet
Sandrine
S
Keck
Simone
S
Fejer
György
G
Huber
Michael
M
Schütze
Nicole
N
Beutler
Bruce
B
Galanos
Chris
C
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D016905:Gram-Negative Bacterial Infections / Q000378:metabolism*; D006801:Humans; D007107:Immune System; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism*; D051218:Lymphocyte Antigen 96; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D008070:Lipopolysaccharides; C411728:Ly96 protein, mouse; D051218:Lymphocyte Antigen 96; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D018664:Interleukin-12; D007371:Interferon-gamma