A shortcut mechanism of innate immune defense by a solitary PRR

Abstract

Event Abstract Back to Event A shortcut mechanism of innate immune defense by a solitary PRR Jeak Ling Ding1* 1 National University of Singapore, Biological Sciences, Singapore The accepted paradigm about an innate immune response is a multi-stepped process - from recognition of the invading microbe by pathogen-recognition receptors (PRRs) to signal transduction, to the production of antimicrobial effectors by the immune cells. Contrary to this belief, we found that a PRR can act singly via a direct shortcut process, bypassing multiple cascades of reactions. We showed that the extracellular hemoglobin (Hb) acts as a solitary frontline defense PRR, directly recognizing pathogens and eliciting powerful antimicrobial potencies. This innate immune response phenomenon is evolutionarily entrenched for 500 million years, from the limulus to humans. While the invading microbe cleaves the cell-free hemoglobin to extract an iron-rich meal for its survival and further invasion, the host exploits the intruding microbe’s proteases and PAMPs to produce toxic reactive oxygen species (ROS) that effectively kills the pathogen. In this process, the hemoglobin structure-function is rapidly reprogrammed to expose multiple dual antimicrobial activities and its redox reactivity is subsequently suppressed by plasma antioxidants, thus protecting the host from ROS-induced cytotoxicity. Furthermore, we demonstrated that the monocytes efficiently import the redox active Hb via a (a) novel endocrine loop of CD163 receptor recycling and (b) paracrine communication with vascular endothelial cells. Acknowledgements We thank the MoE and A*STAR BMRC for financial support. References Jiang N, Tan NS, Ho B and Ding JL. Respiratory protein-generated reactive oxygen species as an antimicrobial strategy. Nature Immunology 8 (2007): 1114-1122 Du RJ, Ho B and Ding JL. Rapid reprogramming of haemoglobin structure-function exposes multiple dual-antimicrobial potencies. EMBO J 29 (2010): 632-642 Bahl N, Du R, Winarsih I, Ho B, Tucker-Kellogg L, Ho B and Ding JL. Delineation of LPS-binding sites of hemoglobin - from in silico predictions to biophysical characterization. J. Biol. Chem 286 (2011): 37793-37803. Du R, Winarsih I, Ho B and Ding JL. Lipid-free apolipoprotein A1 exerts an antioxidative role against cell-free hemoglobin. Am. J. Clin. Exp. Immunol. 1 (2012): 33-48. Subramanian K, Du RJ, Tan NS, Ho B and Ding JL. CD163 and IgG co-defend against cytotoxic hemoglobin via autocrine and paracrine mechanisms. J. Immunol. (in press) Keywords: Innate immune defense, Pathogen pattern-recognition receptors (PRRs), Hemoglobin, Reactive Oxygen Species, Host-Pathogen Interactions Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Innate immunity Citation: Ding J (2013). A shortcut mechanism of innate immune defense by a solitary PRR. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00433 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 02 Apr 2013; Published Online: 22 Aug 2013. * Correspondence: Prof. Jeak Ling Ding, National University of Singapore, Biological Sciences, Singapore, 117543, Singapore, dbsdjl@nus.edu.sg Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Jeak Ling Ding Google Jeak Ling Ding Google Scholar Jeak Ling Ding PubMed Jeak Ling Ding Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.