Experimental models of acute infection and Toll-like receptor driven septic shock.
Mainly Gram-negative and Gram-positive bacterial infections, but also other infections such as with fungal or viral pathogens, can cause the life-threatening clinical condition of septic shock. Transgression of the host immune response from a local level limited to the pathogen's place of entry to the systemic level is recognised as a major mode of action leading to sepsis. This view has been established upon demonstration of the capacity of specific pathogen-associated molecular patterns (PAMPs) to elicit symptoms of septic shock upon systemic administration. Immune stimulatory PAMPs are agonists of soluble, cytoplasmic, as well as/or cell membrane-anchored and/or -spanning pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs). However, reflection of pathogen-host crosstalk triggering sepsis pathogenesis upon an infection by a host response to challenge with an isolated PAMP is incomplete. Therefore, an experimental model more reflective of pathogen-host interaction requires experimental host confrontation with a specific pathogen in its viable form resulting in a collective stimulation of a variety of specific PRRs. This chapter describes methods to analyse innate pathogen sensing by the host on both a cellular and systemic level.
Institut fuer Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universitaet Muenchen, Trogerstr. 30, D-81675, Munich, Germany.
Ruth
R
Ferstl
Stephan
S
Spiller
Sylvia
S
Fichte
Stefan
S
Dreher
Carsten J
CJ
Kirschning
D000818:Animals; D002478:Cells, Cultured; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D008024:Ligands; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008954:Models, Biological; D012772:Shock, Septic / Q000235:genetics / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D008024:Ligands; D051193:Toll-Like Receptors