We have identified 242 Anopheles gambiae genes from 18 gene families implicated in innate immunity and have detected marked diversification relative to Drosophila melanogaster. Immune-related gene families involved in recognition, signal modulation, and effector systems show a marked deficit of orthologs and excessive gene expansions, possibly reflecting selection pressures from different pathogens encountered in these insects' very different life-styles. In contrast, the multifunctional Toll signal transduction pathway is substantially conserved, presumably because of counterselection for developmental stability. Representative expression profiles confirm that sequence diversification is accompanied by specific responses to different immune challenges. Alternative RNA splicing may also contribute to expansion of the immune repertoire.
During a genome-wide RNAi screen, we isolated CG8580 as a gene involved in the innate immune response of Drosophila. CG8580, which we named Akirin, acts in parallel with the NF-κB transcription factor downstream of the Imd pathway and was required for defense against Gram-negative bacteria. Akirin is highly conserved and the human genome contains two homologues, one of which was able to rescue the loss of function phenotype in Drosophila cells. Akirins had a strict nuclear localization. Knockout of both Akirin homologues in mice revealed that one had an essential function downstream of Toll-like receptor, tumor necrosis factor and interleukin 1-β (IL-1β) signaling pathways leading to the production of IL-6. Thus, Akirin is a conserved nuclear factor required for innate immune responses.The innate immune system shields all metazoans against invading microorganisms. This well conserved defense mechanism relies on host-pathogen interactions between nonclonally distributed pattern recognition receptors in the host and pathogen-associated molecular patterns in microbes (reviewed in1-4). In contrast, the acquired immune system, based on selection of lymphocytes and their antigen-specific receptors, is specific to vertebrates. Drosophila has become an attractive model organism for the study of the innate immune system due to its well-established genetics, the absence of an acquired immune system and the striking conservation between its immune system and many mammalian Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms Correspondence should be addressed to J-MR (e-mail: JM.Reichhart@ibmc.u-strasbg.fr). 4 current address, Graduate School of Pharmaceutical Sciences, Tohoku University, Aramaki Aoba-ku, Sendai, 980-8578, Japan 5 AG and KM contributed equally to this work. AUTHOR CONTRIBUTIONS A.G., V.G., L.E.-C., and D.K. did the Drosophila experiments. K.M. and O.T. did the mouse experiments. S.A., M.B., O.T. and JM.R. conceived and directed the experiments, A.G., O.T., JA.H. and JM.R. wrote the paper. All authors contributed to manuscript criticism. Despite more than ten years of research since the initial discovery of the Imd mutation, the pathway that took its name is still not fully understood. We undertook a functional genome- (Fig. 1). The conservation is highest for the putative C and N-terminal domains. All sequences show a clear nuclear localization signal (NLS) located between residues 24 and 29 at the N-terminus ( Supplementary Fig. 1 online). We renamed the gene Akirin (Akirin1 and Akirin2 in the case of vertebrates) from the japanese `akiraka ni suru', which means `making things clear'. HHS Public Access RESULTS Identification of Drosophila and mice Akirin homologues Akirins are ubiquitously expressed nuclear proteinsMicroarray data in Flybase35 indicate that DmAkirin expression is ubiquitous. Similarly, an an...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.