Increased PD-L1 expression and PD-L1/CD86 ratio on macrophages infected with Neisseria gonorrhoeae contributes to the functional Suppression of T-cell responses.

Abstract

Event Abstract Back to Event Increased PD-L1 expression and PD-L1/CD86 ratio on macrophages infected with Neisseria gonorrhoeae contributes to the functional Suppression of T-cell responses. Alejandro Escobar1*, Carolina Ortiz1, Killen Garcia1, Paula Rodas2 and Claudio Acuña-Castillo3 1 Universidad de Chile, Instituto de Investigación en Ciencias Odontológicas, Chile 2 Universidad Andres Bello, Center for Integrative Medicine and Innovative Science, Chile 3 Universidad de Santiago, Chile Neisseria gonorrhoeae is the etiological agent of the sexually transmitted disease gonorrhoea, which is widespread throughout the world. Infections with Neisseria gonorrhoeae do not improve immune response in patients with re-infection, suggesting that gonococcus displays several mechanisms to evade immune response and survive in the host. Our data indicate that Neisseria gonorrhoeae is able to suppress the protective immune response in macrophages, polarized them towards an immunoregulatory profile characterized by up-regulation of M2-Macrophage-associated markers and IL-10. Considering there are numerous reports indicating the capacity of Intracellular pathogens like Mycobacteria to impair innate and adaptative immune response using inhibitory role played by Programmed Death 1 and Programmed Death Ligand 1 (PD-1/PD-L1) interactions, in this study, we evaluated surface co-stimulatory (CD86, CD40) and co-inhibitory (PD-L1) markers expression and allostimulatory capacity in macrophages infected with Neisseria gonorrhoeae. Results showed that Neisseria gonorrhoeae was not able to induce the co-stimulatory CD86 neither CD40. However, we found a significant up-regulation of PD-L1 in macrophages upon gonococcal infection. PD-L1/CD86 ratio was increased and positively correlated with PD-L1 expression on macrophages. Allostimulatory capacity of macrophages was impaired and inversely correlated with PD-L1 expression and PD-L1/CD86 ratio. Finally, to verify that the cell contact–dependent inhibition of proliferation was due to macrophage´s PD-L1, we set up a co-culture in the presence of blocking antibody to PD-L1 and to IL-10. We showed that only PD-L1 blocking restored T-cell proliferation. These findings suggested that the effect of inhibitory marker PD-L1 overwhelmed the effect of co-stimulatory markers and down-regulated macrophage-T activation in presence of Neisseria gonorrhoeae infection. This study has important implications for understanding the mechanisms of clearance versus long-term persistence of N. gonorroheae infection and might be applicable for the development of new therapeutic strategies. Acknowledgements Dirección Investigación Facultad Odontología Universidad de Chile. Keywords: Neisseria gonorrhoeae, Macrophages, PD-L1, alloprolifertion, Immune Evasion 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: Escobar A, Ortiz C, Garcia K, Rodas P and Acuña-Castillo C (2015). Increased PD-L1 expression and PD-L1/CD86 ratio on macrophages infected with Neisseria gonorrhoeae contributes to the functional Suppression of T-cell responses.. 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.2015.05.00303 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: 15 Apr 2015; Published Online: 15 Sep 2015. * Correspondence: Dr. Alejandro Escobar, Universidad de Chile, Instituto de Investigación en Ciencias Odontológicas, Santiago, Chile, janodvm@gmail.com 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 Alejandro Escobar Carolina Ortiz Killen Garcia Paula Rodas Claudio Acuña-Castillo Google Alejandro Escobar Carolina Ortiz Killen Garcia Paula Rodas Claudio Acuña-Castillo Google Scholar Alejandro Escobar Carolina Ortiz Killen Garcia Paula Rodas Claudio Acuña-Castillo PubMed Alejandro Escobar Carolina Ortiz Killen Garcia Paula Rodas Claudio Acuña-Castillo 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.