Human metapneumovirus infection activates the TSLP pathway that drives excessive pulmonary inflammation and viral replication in mice

Abstract

Event Abstract Back to Event Human metapneumovirus infection activates the TSLP pathway that drives excessive pulmonary inflammation and viral replication in mice Pablo F. Céspedes1, Margarita K. Lay1*, Christian E. Palavecino1, Miguel Á. León1, Rodrigo A. Díaz1, Francisco J. Salazar1, Gonzalo P. Méndez2, Susan M. Bueno3, 4 and Alexis M. Kalergis1, 4, 5* 1 Pontificia Universidad Católica de Chile, Molecular Genetics and Microbiology Department, Chile 2 Pontificia Universidad Católica de Chile, Pathology, Medicine, Chile 3 Pontificia Universidad Católica de Chile, Molecular Genetics and Microbiology Department, Chile 4 INSERM U1064, France 5 Pontificia Universidad Católica de Chile, Rheumatology, Medicine, Chile Human metapneumovirus (hMPV) is a leading cause of acute respiratory tract infections in children and the elderly. The mechanism by which this virus triggers an inflammatory response still remains unknown. Here, we evaluated whether the thymic stromal lymphopoietin (TSLP) pathway contributes to lung inflammation upon hMPV infection. We found that hMPV infection promotes TSLP expression both in human airway epithelial cells and in the mouse lung. hMPV infection induced lung infiltration of OX40L+CD11b+ DCs. Mice lacking the TSLP receptor deficient mice (tslpr−/−) showed reduced lung inflammation and hMPV replication. These mice displayed a decreased number of neutrophils as well a reduction in levels of thymus and activation-regulated chemokine/CCL17, IL-5, IL-13, and TNF-α in the airways upon hMPV infection. Furthermore, a higher frequency of CD4+ and CD8+ T cells was found in tslpr−/− mice compared to WT mice, which could contribute to controlling viral spread. Depletion of neutrophils in WT and tslpr−/− mice decreased inflammation and hMPV replication. Remarkably, blockage of TSLP or OX40L with specific Abs reduced lung inflammation and viral replication following hMPV challenge in mice. Altogether, these results suggest that activation of the TSLP pathway is pivotal in the development of pulmonary pathology and pulmonary hMPV replication. Acknowledgements This research was supported by CONICYT grants: FONDECYT POSTDOCTORADO N° 3120019; N° 3140455, and FONDECYT grant 1070352; FONDEF D061008; and the Millennium Institute on Immunology and Immunotherapy (P07/088-F). Keywords: TSLP, HMPV, OX40 Ligand, Lung, Inflammation Conference: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015. Presentation Type: Oral Presentation Topic: Infectious and parasitic diseases Citation: Céspedes PF, Lay MK, Palavecino CE, León MÁ, Díaz RA, Salazar FJ, Méndez GP, Bueno SM and Kalergis AM (2015). Human metapneumovirus infection activates the TSLP pathway that drives excessive pulmonary inflammation and viral replication in mice. Front. Immunol. Conference Abstract: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología. doi: 10.3389/conf.fimmu.2015.05.00316 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: 14 May 2015; Published Online: 15 Sep 2015. * Correspondence: Dr. Margarita K Lay, Pontificia Universidad Católica de Chile, Molecular Genetics and Microbiology Department, Santiago, Chile, margarita.lay@uantof.cl Dr. Alexis M Kalergis, Pontificia Universidad Católica de Chile, Molecular Genetics and Microbiology Department, Santiago, Chile, akalergis@bio.puc.cl 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 Pablo F Céspedes Margarita K Lay Christian E Palavecino Miguel Á León Rodrigo A Díaz Francisco J Salazar Gonzalo P Méndez Susan M Bueno Alexis M Kalergis Google Pablo F Céspedes Margarita K Lay Christian E Palavecino Miguel Á León Rodrigo A Díaz Francisco J Salazar Gonzalo P Méndez Susan M Bueno Alexis M Kalergis Google Scholar Pablo F Céspedes Margarita K Lay Christian E Palavecino Miguel Á León Rodrigo A Díaz Francisco J Salazar Gonzalo P Méndez Susan M Bueno Alexis M Kalergis PubMed Pablo F Céspedes Margarita K Lay Christian E Palavecino Miguel Á León Rodrigo A Díaz Francisco J Salazar Gonzalo P Méndez Susan M Bueno Alexis M Kalergis 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.