The role of complement in danger sensing and transmission

Immunol Res. 2006;34(2):157-76. doi: 10.1385/IR:34:2:157.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Complement Activation
  • Complement System Proteins / immunology*
  • Dendritic Cells / immunology
  • Humans
  • Immunity, Innate*
  • Lung / immunology
  • Receptors, Complement / metabolism
  • Signal Transduction
  • Toll-Like Receptors / immunology


  • Receptors, Complement
  • Toll-Like Receptors
  • Complement System Proteins