MyD88 signaling in CD11b+ myeloid cells protects against colonic adenoma formation

Abstract

Event Abstract Back to Event MyD88 signaling in CD11b+ myeloid cells protects against colonic adenoma formation Rosalba Salcedo1*, Ren Ming Dai1, Jonathan Badger1 and Giorgio Trinchieri1 1 National Cancer Institute, National Institute of Heath USA, Cancer and Inflammation Program, United States Myeloid differentiation factor 88 (MyD88) is an important signaling molecule which senses microbial products via recognition mediated by toll-like receptors. Using the AOM/DSS model of colitis, we previously described that the inability of Myd88-/- mice to heal ulcers induced upon DSS, creates an inflammatory microenvironment resulting in increase in adenoma formation. To identify the cellular compartment involved in MyD88 protection of colitis and colon cancer, we generated bone marrow chimeras and found that the hematopoietic compartments contribute to the protective role of MyD88 against colon cancer. Specific deletion of Myd88 in Cd11b+ cells (Myd88CD11b Δ/Δ ) resulted increased colonic adenoma formation in response to AOM-DSS treatment. In contrast, deletion of Myd88 in B cells, T cells and dendritic cells did not impact the formation of colonic polyps. The gene expression profile of sorted myeloid cells from inflamed colons indicated that Myd88 deficiency resulted in increased expression of acute inflammatory markers including S100a8, S100a9, Il1 and Il6. Notably, in the absence of Myd88, and upon exposure of the colonic mucosa to microbial translocation, compensatory antimicrobial mechanisms were activated in myeloid cells including enhanced expression of microbial peptide receptor genes Fpr1 and Fpr2, and the siderophore sequestering Lipocalin-2 (Lnc2). Importantly, Myd88-/- and Myd88CD11b Δ/Δ animals carry a pro-tumorigenic microbiota which was transmissible to wild type animals, since post cohousing and in response to AOM/DSS treatment, wild type animals developed a remarkable increase in multiplicity and size of colonic adenomas, relative to segregated controls. Cohousing resulted in evident but partially transient changes in microbiota composition in both wild type and mutant mice. AOM/DSS treatment resulted in reamarkable disbiosis and concomitant increased adenoma formation. This data indicates that deficiency of Myd88 in myeloid cells favors the development of a pro-tumorogenic microbiome, which is transmissible and which under the exposure to a carcinogen and under chronic inflammatory conditions results in increased tumor development. Keywords: Colitis, Colonic adenomas, microbiome, MyD88, Myeloid Cells 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: Mucosal Immunity and the microbiome Citation: Salcedo R, Dai R, Badger J and Trinchieri G (2015). MyD88 signaling in CD11b+ myeloid cells protects against colonic adenoma formation. 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.2015.05.00332 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: 31 May 2015; Published Online: 15 Sep 2015. * Correspondence: Dr. Rosalba Salcedo, National Cancer Institute, National Institute of Heath USA, Cancer and Inflammation Program, Bethesda, Maryland, 20892, United States, salcedor@mail.nih.gov 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 Rosalba Salcedo Ren Ming Dai Jonathan Badger Giorgio Trinchieri Google Rosalba Salcedo Ren Ming Dai Jonathan Badger Giorgio Trinchieri Google Scholar Rosalba Salcedo Ren Ming Dai Jonathan Badger Giorgio Trinchieri PubMed Rosalba Salcedo Ren Ming Dai Jonathan Badger Giorgio Trinchieri 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.