The immune system has to recognize potential threats from microbes and react quickly and specifically. Researchers have now shown human immune cells integrate multiple signals obtained by 'tasting' their microbial invader through sensors known as Toll-like receptors (TLRs), according to the August 2005 issue of Nature Immunology.
By using combinations of different TLRs, including those on the cell surface and internal receptors within specialized compartments where engulfed bacteria or viruses reside, these human dendritic cells alert the rest of the immune system to even tiny amounts of pathogen. Dendritic cells are known to play a key role in immunity by presenting antigens to prime specific immune responses as well as secreting molecules, known as cytokines, that signal 'danger'. Lanzavecchia and colleagues show activation of multiple TLRs results in amplified signals and lead to higher production of the cytokines known as interleukins 12 and 23. This action recruits more immune cells to the infected area and arms them against perceived intracellular threats. Such responses are critical for pathogens like the tuberculosis bacteria or viruses. This type of immune response, since it directs immune cells to seek out and kill infected cells, needs to be tightly controlled. The use of multiple signals, akin to dual keys, affords the immune system both the sensitivity and specificity required for such reactions. Author contact: Antonio Lanzavecchia (Institute for Research in Biomedicine, Bellinzona, Switzerland) E-mail: lanzavecchia@irb.unisi.ch Additional contact for comment on the paper: Bernard Malissen (Universite de la Mediterranee, Marseille, France) E-mail: bernardm@ciml.univ-mrs.fr Also published online. (C) Nature Immunology press release.
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