Interferon-gamma-activated macrophages infected with Burkholderia cenocepacia process and present bacterial antigens to T-cells by class I and II major histocompatibility complex molecules

Burkholderia cenocepacia is an emerging opportunistic pathogen for people with cystic fibrosis and chronic granulomatous disease. Intracellular survival in macrophages within a membrane-bound vacuole (BcCV) that delays acidification and maturation into lysosomes is a hallmark of B. cenocepacia infec...

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Main Authors: Roberto Rosales-Reyes, Paola Garza-Villafuerte, Daniela Vences-Vences, Daniel F. Aubert, Rubi Aca-Teutle, Vianney F. Ortiz-Navarrete, Laura C. Bonifaz, Julio Cesar Carrero-Sánchez, Alfonso Olivos-García, Miguel A. Valvano, José Ignacio Santos-Preciado
Format: Article
Language:English
Published: Taylor & Francis Group 2020-01-01
Series:Emerging Microbes and Infections
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Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2020.1818632
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author Roberto Rosales-Reyes
Paola Garza-Villafuerte
Daniela Vences-Vences
Daniel F. Aubert
Rubi Aca-Teutle
Vianney F. Ortiz-Navarrete
Laura C. Bonifaz
Julio Cesar Carrero-Sánchez
Alfonso Olivos-García
Miguel A. Valvano
José Ignacio Santos-Preciado
author_facet Roberto Rosales-Reyes
Paola Garza-Villafuerte
Daniela Vences-Vences
Daniel F. Aubert
Rubi Aca-Teutle
Vianney F. Ortiz-Navarrete
Laura C. Bonifaz
Julio Cesar Carrero-Sánchez
Alfonso Olivos-García
Miguel A. Valvano
José Ignacio Santos-Preciado
author_sort Roberto Rosales-Reyes
collection DOAJ
description Burkholderia cenocepacia is an emerging opportunistic pathogen for people with cystic fibrosis and chronic granulomatous disease. Intracellular survival in macrophages within a membrane-bound vacuole (BcCV) that delays acidification and maturation into lysosomes is a hallmark of B. cenocepacia infection. Intracellular B. cenocepacia induce an inflammatory response leading to macrophage cell death by pyroptosis through the secretion of a bacterial deamidase that results in the activation of the pyrin inflammasome. However, how or whether infected macrophages can process and present B. cenocepacia antigens to activate T-cells has not been explored. Engulfed bacterial protein antigens are cleaved into small peptides in the late endosomal major histocompatibility class II complex (MHC) compartment (MIIC). Here, we demonstrate that BcCVs and MIICs have overlapping features and that interferon-gamma-activated macrophages infected with B. cenocepacia can process bacterial antigens for presentation by class II MHC molecules to CD4+ T-cells and by class I MHC molecules to CD8+ T-cells. Infected macrophages also release processed bacterial peptides into the extracellular medium, stabilizing empty class I MHC molecules of bystander cells. Together, we conclude that BcCVs acquire MIIC characteristics, supporting the notion that macrophages infected with B. cenocepacia contribute to establishing an adaptive immune response against the pathogen.
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spelling doaj-art-45e072e3a63d438f9918edc68a695a6b2025-08-20T02:26:36ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512020-01-01912000201210.1080/22221751.2020.1818632Interferon-gamma-activated macrophages infected with Burkholderia cenocepacia process and present bacterial antigens to T-cells by class I and II major histocompatibility complex moleculesRoberto Rosales-Reyes0Paola Garza-Villafuerte1Daniela Vences-Vences2Daniel F. Aubert3Rubi Aca-Teutle4Vianney F. Ortiz-Navarrete5Laura C. Bonifaz6Julio Cesar Carrero-Sánchez7Alfonso Olivos-García8Miguel A. Valvano9José Ignacio Santos-Preciado10Facultad de Medicina, Unidad de Investigación en Medicina Experimental, Universidad Nacional Autónoma de México, Mexico City, MéxicoFacultad de Medicina, Unidad de Investigación en Medicina Experimental, Universidad Nacional Autónoma de México, Mexico City, MéxicoFacultad de Medicina, Unidad de Investigación en Medicina Experimental, Universidad Nacional Autónoma de México, Mexico City, MéxicoDepartment of Microbiology and Immunology, The University of Western Ontario, London, CanadaFacultad de Medicina, Unidad de Investigación en Medicina Experimental, Universidad Nacional Autónoma de México, Mexico City, MéxicoDepartamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del IPN, Mexico City, MéxicoUnidad de Investigación Médica en Inmunoquímica Hospital de Especialidades Centro Médico Nacional Siglo XXI, IMSS, Mexico City, MexicoInstituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, MexicoFacultad de Medicina, Unidad de Investigación en Medicina Experimental, Universidad Nacional Autónoma de México, Mexico City, MéxicoDepartment of Microbiology and Immunology, The University of Western Ontario, London, CanadaFacultad de Medicina, Unidad de Investigación en Medicina Experimental, Universidad Nacional Autónoma de México, Mexico City, MéxicoBurkholderia cenocepacia is an emerging opportunistic pathogen for people with cystic fibrosis and chronic granulomatous disease. Intracellular survival in macrophages within a membrane-bound vacuole (BcCV) that delays acidification and maturation into lysosomes is a hallmark of B. cenocepacia infection. Intracellular B. cenocepacia induce an inflammatory response leading to macrophage cell death by pyroptosis through the secretion of a bacterial deamidase that results in the activation of the pyrin inflammasome. However, how or whether infected macrophages can process and present B. cenocepacia antigens to activate T-cells has not been explored. Engulfed bacterial protein antigens are cleaved into small peptides in the late endosomal major histocompatibility class II complex (MHC) compartment (MIIC). Here, we demonstrate that BcCVs and MIICs have overlapping features and that interferon-gamma-activated macrophages infected with B. cenocepacia can process bacterial antigens for presentation by class II MHC molecules to CD4+ T-cells and by class I MHC molecules to CD8+ T-cells. Infected macrophages also release processed bacterial peptides into the extracellular medium, stabilizing empty class I MHC molecules of bystander cells. Together, we conclude that BcCVs acquire MIIC characteristics, supporting the notion that macrophages infected with B. cenocepacia contribute to establishing an adaptive immune response against the pathogen.https://www.tandfonline.com/doi/10.1080/22221751.2020.1818632Burkholderia cepacia complexT-cell activationantigen processingMIICRab7Type 6 secretion
spellingShingle Roberto Rosales-Reyes
Paola Garza-Villafuerte
Daniela Vences-Vences
Daniel F. Aubert
Rubi Aca-Teutle
Vianney F. Ortiz-Navarrete
Laura C. Bonifaz
Julio Cesar Carrero-Sánchez
Alfonso Olivos-García
Miguel A. Valvano
José Ignacio Santos-Preciado
Interferon-gamma-activated macrophages infected with Burkholderia cenocepacia process and present bacterial antigens to T-cells by class I and II major histocompatibility complex molecules
Emerging Microbes and Infections
Burkholderia cepacia complex
T-cell activation
antigen processing
MIIC
Rab7
Type 6 secretion
title Interferon-gamma-activated macrophages infected with Burkholderia cenocepacia process and present bacterial antigens to T-cells by class I and II major histocompatibility complex molecules
title_full Interferon-gamma-activated macrophages infected with Burkholderia cenocepacia process and present bacterial antigens to T-cells by class I and II major histocompatibility complex molecules
title_fullStr Interferon-gamma-activated macrophages infected with Burkholderia cenocepacia process and present bacterial antigens to T-cells by class I and II major histocompatibility complex molecules
title_full_unstemmed Interferon-gamma-activated macrophages infected with Burkholderia cenocepacia process and present bacterial antigens to T-cells by class I and II major histocompatibility complex molecules
title_short Interferon-gamma-activated macrophages infected with Burkholderia cenocepacia process and present bacterial antigens to T-cells by class I and II major histocompatibility complex molecules
title_sort interferon gamma activated macrophages infected with burkholderia cenocepacia process and present bacterial antigens to t cells by class i and ii major histocompatibility complex molecules
topic Burkholderia cepacia complex
T-cell activation
antigen processing
MIIC
Rab7
Type 6 secretion
url https://www.tandfonline.com/doi/10.1080/22221751.2020.1818632
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