Recognizing the First Responders

Abstract

![Figure][1] CREDIT: C. BICKEL/ SCIENCE 2009 marked the 20th anniversary of Charles Janeway's seminal hypothesis that the body's response to infection is mediated by receptors on immune cells that recognize microbial patterns. Before this, immunologists primarily studied T and B lymphocytes, which express highly specific antigen receptors, but Janeway's prediction that direct microbial detection by immune cells other than lymphocytes precedes and is required for subsequent lymphocyte activation helped open the door to a new field of immunology: the study of the innate immune system. Much work over the past 20 years has borne out Janeway's predictions, and the fundamental importance of the innate immune system is now well established. The collection of articles in this issue encompasses both the primary focus of the field over the past two decades—the molecular dissection of microbial recognition—and also more recent areas of interest, including the interaction between the innate and adaptive immune systems and the identification of noninfectious diseases associated with innate immune system function. A Perspective by Rehwinkel and Reis e Sousa (p. [284][2]) discusses recent advances in the elucidation of how members of the RIG-I–like receptor family distinguish viral nucleic acids from the abundance of host nucleic acids present in an infected cell. The ability to specifically recognize viral nucleic acids is critical for proper immune responses to viral infection. Another family of microbial receptors, the NLRs, is discussed in a Review by Ting and colleagues (p. [286][3]). These receptors have received a great deal of recent attention because of their role in the inflammatory protein complex termed the inflammasome; however, as Ting et al. present, mounting evidence indicates that their inflammasome-independent functions may play an equally important role in the responses to pathogens by the innate immune system. How microbial recognition by the innate immune system couples to the activation of T and B lymphocytes of the adaptive immune system is discussed in a Review by Iwasaki and Medzhitov (p. [291][4]). This Review highlights the fact that we still have much to learn about this cooperation, particularly in cases when the microbes are being sensed within the cell. Although it is well recognized that the innate immune system is critical for responses to microbial insults, research has also emerged demonstrating that the innate immune system may play an unexpected role in diseases not classically associated with the immune system. A Review by Schroder and colleagues (p. [296][5]) explores one example: the role of the innate immune receptor NLRP3 in the metabolic diseases type 2 diabetes and gout. A collection of articles at Science Signaling ([www.sciencemag.org/special/immunity][6]) highlights immune responses to pathogens, the mechanism of interleukin-1 signaling, and aspects of the control of the adaptive immune response by dendritic cells. Together, these articles highlight how far our understanding of the innate immune system has come in the past 20 years and suggest areas where the important discoveries of the next decades are likely to come. [1]: pending:yes [2]: /lookup/doi/10.1126/science.1185068 [3]: /lookup/volpage/327/286?iss=5963 [4]: /lookup/volpage/327/291 [5]: /lookup/volpage/327/296?iss=5963 [6]: http://www.sciencemag.org/special/immunity