The complement system has a critical role in the inflammatory reaction that follows influenza virus infection

Abstract

Event Abstract Back to Event The complement system has a critical role in the inflammatory reaction that follows influenza virus infection Santiago F. Gonzalez1*, Caroline Herndon2, Juan Ortin3 and Michael Carroll2 1 Institute for Research in Biomedicine, Switzerland 2 Harvard Medical School, United States 3 Centro Nacional de Biotecnologia, Spain Influenza virus represents a major worldwide health problem and influenza pandemics are amongst the deadliest disease events for humans and many animal species. Previous studies have indicated a role for the complement system and it’s receptors, in the immune response to influenza virus. However, the role of the complement system in the initiation of the influenza virus infection and the cytokine storm that follows the infection remains unclear. In this work we evaluated the functions of some of the major complement proteins in the response to influenza using mice deficient in C3, C1q and C4. We observed that all of the complement deficient strains show higher mortality and morbidity rates compared to wild type animals after a sublethal infection with influenza. In addition, complement C3 was necessary to promote the phagocytosis of the virus and/or viral infected cells by the major phagocytic cells in the lungs (alveolar macrophages, neutrophils and monocytes) at early time points after infection. Interestingly, we also observed a clear reduction in the number of viral positive respiratory dendritic cells in the complement deficient animals compared to B6 controls that correlate with a deficient T cell activation in the draining mediastinal lymph node. However, the levels of the pro-inflammatory cytokines IL1β, MCP1, MIP2 and TNFα in the lung of mice at day 2 post-infection were significantly higher in complement deficient C3 and C4 animals compared with the control group. From these results we can conclude that the pronounced decrease in the phagocytic activity of lymphocytes in the lungs from complement deficient animals facilitates the dissemination of the virus and increases the epithelial damage augmenting at the same time the cytokine storm that leads to the dead of the animal. In addition, the adaptive immune responses are impaired mainly due to a deficient activation of the migratory respiratory dendritic cells that fail to activate efficiently antiviral T cell responses in the draining lymph node. Keywords: complement system, Influenza virus infection, C3, Inflammation, c1q Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Host-pathogen interactions Citation: F. Gonzalez S, Herndon C, Ortin J and Carroll M (2013). The complement system has a critical role in the inflammatory reaction that follows influenza virus infection. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00816 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: 19 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Santiago F. Gonzalez, Institute for Research in Biomedicine, Bellinzona, Switzerland, santiago.gonzalez@irb.usi.ch 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 Santiago F. Gonzalez Caroline Herndon Juan Ortin Michael Carroll Google Santiago F. Gonzalez Caroline Herndon Juan Ortin Michael Carroll Google Scholar Santiago F. Gonzalez Caroline Herndon Juan Ortin Michael Carroll PubMed Santiago F. Gonzalez Caroline Herndon Juan Ortin Michael Carroll 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.