Sepsis and evolution of the innate immune response.
OBJECTIVE
To review the role of the Toll-like receptors (TLR) as the principal sensors used by the innate immune system in the context of the pathologic processes underlying sepsis and septic shock.


METHODS
Literature review.


METHODS
Through the Toll-like receptors, macrophages and other defensive cells "see" endotoxin (TLR4), peptidoglycan (TLR2), and bacterial DNA (TLR9). Representatives of the family predated the divergence of plants and animals and, at that time, had already acquired a defensive function. The strengths and liabilities of the innate immune system, which defends against infection and which also may cause shock and death, are rooted in its ancient origins. In the current era of shock research, the nature of the signals that Toll-like receptors transduce and the effects of genetic variation on microbial sensing are two major challenges.
Beutler
B
B
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA. bruce@scripps.edu
Poltorak
A
A
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D005075:Biological Evolution; D004269:DNA, Bacterial / Q000276:immunology; D029721:Drosophila Proteins; D014644:Genetic Variation / Q000235:genetics / Q000276:immunology; D006801:Humans; D051218:Lymphocyte Antigen 96; D008214:Lymphocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D010457:Peptidoglycan / Q000276:immunology; D010944:Plants / Q000276:immunology; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D018805:Sepsis / Q000276:immunology* / Q000382:microbiology; D012772:Shock, Septic / Q000276:immunology* / Q000382:microbiology; D015398:Signal Transduction / Q000276:immunology; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors
D000906:Antibodies; D000954:Antigens, Surface; D004269:DNA, Bacterial; D029721:Drosophila Proteins; C495377:LY96 protein, human; D051218:Lymphocyte Antigen 96; D008562:Membrane Glycoproteins; D010457:Peptidoglycan; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors