The role of Toll-like receptors and Nod proteins in bacterial infection.
Our understanding of innate immunity in mammals has greatly expanded following the discovery of the family of membrane-bound receptors, called the Toll-like receptors (TLRs). More recently, the nucleotide-binding oligomerisation domain (Nod) molecules, Nod1 and Nod2, which are cytoplasmic surveillance proteins, have also been shown to be involved in the innate immune response. These two classes of detection molecules, classified as "pattern recognition receptors" (PRRs), detect microbial ligands in order to initiate a defense response to fight infectious disease. These microbial ligands or "pathogen-associated molecular patterns" (PAMPs), detected by TLRs and Nods are often structural components of the microorganism that are not subject to much variation. These include such factors as lipopolysaccharide (LPS) and peptidoglycan from the cell walls of bacteria. In order to understand the role of TLRs and Nod proteins in infectious disease in vivo it is important to define the site of interaction between PRRs and PAMPS. Additionally, the challenge of mice deficient in the various PRRs in natural infection models will help to decipher the contribution of these molecules not only in the innate immune response against pathogen infection but also how these proteins may instruct the adaptive immune response in order to have a tailored immune response against a particular microbe.
Philpott
Dana J
DJ
Immunité Innée et Signalisation, Institut Pasteur, 28 rue du Dr. Roux, 75724 Paris 15, France. philpott@pasteur.fr
Girardin
Stephen E
SE
D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology / Q000502:physiology; D000818:Animals; D001424:Bacterial Infections / Q000276:immunology*; D029721:Drosophila Proteins / Q000276:immunology / Q000502:physiology*; D016905:Gram-Negative Bacterial Infections / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000502:physiology*; D016547:Kinesins; D008562:Membrane Glycoproteins / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008868:Microtubule Proteins / Q000276:immunology / Q000502:physiology*; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D011956:Receptors, Cell Surface / Q000276:immunology / Q000502:physiology*; D051193:Toll-Like Receptors
D048868:Adaptor Proteins, Signal Transducing; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008868:Microtubule Proteins; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; C080298:Nod protein, Drosophila; D016547:Kinesins