The role of complement in danger sensing and transmission.
Self-non-self discrimination has long been considered the main function of the immune system. Increasing evidence supports the view of the immune system as a network of complex danger sensors and transmitters in which self-non-self discrimination is only one facet. To meet the challenge of danger sensing, the immune system carries a large stock of germline-encoded, highly conserved molecules that can recognize microbial as well as modified host structures. Among those are the Toll-like receptors (TLR), which comprise a dozen membrane-bound pattern-recognition receptors that directly link danger recognition to danger transmission through activation of several distinct cellular signaling pathways. Here, I discuss the function and biology of a complex, evolutionary ancient system, the complement system, which has long been considered critical to host defense. In contrast to TLRs, the complement system senses danger by a panel of soluble molecules that can directly bind to specific complement receptors and/or initiate a complex cascade of proteolytic events that lead to the generation of soluble complement fragments able to bind to another, distinct set of specific complement receptors. As I will outline in this review, complement- mediated danger sensing and the complex transition of this information into distinct cellular activation profiles is critical for tissue homeostasis under steady-state conditions and in response to infection and cell injury. Furthermore, I will discuss recent findings that support a concept of intense cross-talk between the complement system and TLRs, which defines the quality and the magnitude of immune responses in vivo.
Köhl
Jörg
J
Division of Molecular Immunology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA. Joerg.Koehl@chmcc.org
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D003167:Complement Activation; D003165:Complement System Proteins / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D008168:Lung / Q000276:immunology; D011951:Receptors, Complement / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000276:immunology
D011951:Receptors, Complement; D051193:Toll-Like Receptors; D003165:Complement System Proteins