Toll-Like Receptors

  • Jérôme Pugin
Part of the Perspectives on Critical Care Infectious Diseases book series (CCID, volume 2)


Molecular recognition of bacterial, non-self molecules is a critical event in the initiation of innate immune responses. This important function has been conserved throughout evolution from insects to humans (1–4). Several host cell surface receptors mediating this function have been identified. Some of these molecules, such as the mannose receptor, the scavenger receptor and complement receptors bind bacteria and bacterial molecules, enhance the cell’s ability to ingest and clear out the invading microbe, but do not mediate cell activation (1, 5). Another class of molecules of the innate immunity is composed of circulating soluble proteins, generally acute phase reactants, which recognize and bind bacteria and bacterial molecules with high affinity. Their function is to opsonize the microbe (lipopolysaccharide (LPS)-binding protein, LBP; soluble CD14, sCD14, complement fractions, C-reactive protein), and to shuttle bacterial molecules such as LPS to cell surface receptors or to high density lipoproteins (LBP, sCD14). Some of these proteins, such as the bactericidal/permeability increasing (BPI) protein, have direct bactericidal activity (1). The third class of molecules of the innate immunity includes cell surface receptors which recognize and bind whole bacteria or conserved bacterial molecules such as LPS. Receptors responding to this definition are CD14 and the newly discovered Toll-like receptors (TLRs), reviewed in (2, 4, 6–16). Importantly, engagement of these receptors induces the activation of immune cells with the production of a wide variety of responses including the secretion of cytokines, chemokines, the production of oxygen and nitrogen radicals, pro-coagulants, proteolytic enzymes, etc. Engagement of both these soluble and cellular responses corresponds to the first line of defense, i.e. the innate limb of the immunity, and is aimed at controlling the invading microorganism and eventually killing it. It also generates inflammation, local or systemic depending on the site of the infection. Inadequacy in the magnitude, timing or localization of this response may lead to pathological conditions such as the sepsis syndrome (17, 18).


Septic Shock TLR4 Gene Secretory Leukocyte Protease Inhibitor Bacterial Ligand Bacterial Molecule 
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© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Jérôme Pugin
    • 1
  1. 1.Division of Medical Intensive CareUniversity Hospital of GenevaGenevaSwitzerland

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