High Glucose Concentrations Impair the Processing and Presentation of <i>Mycobacterium tuberculosis</i> Antigens In Vitro
Type 2 diabetes is an established risk factor for tuberculosis, but the underlying mechanisms are largely unknown. We established an in vitro model to analyze the effect of high glucose concentrations in antigen processing and presentation in antigen-presenting cells. Human monocyte-derived macropha...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/12/1763 |
| _version_ | 1827673962311581696 |
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| author | Guadalupe Monroy-Mérida Silvia Guzmán-Beltrán Fernando Hernández Teresa Santos-Mendoza Karen Bobadilla |
| author_facet | Guadalupe Monroy-Mérida Silvia Guzmán-Beltrán Fernando Hernández Teresa Santos-Mendoza Karen Bobadilla |
| author_sort | Guadalupe Monroy-Mérida |
| collection | DOAJ |
| description | Type 2 diabetes is an established risk factor for tuberculosis, but the underlying mechanisms are largely unknown. We established an in vitro model to analyze the effect of high glucose concentrations in antigen processing and presentation in antigen-presenting cells. Human monocyte-derived macrophages (MDMs) were exposed to high (11 mM and 30 mM) and low (5.5 mM) glucose concentrations and infected with <i>Mycobacterium tuberculosis (Mtb)</i>. Flow cytometry was used to analyze the effect of high glucose concentrations in histocompatibility complex (MHC) class II molecules (HLA-DR) and co-stimulatory molecules (CD80 and CD86), indispensable for an adequate antigenic presentation and CD4+ T cell activation. HLA-DR and CD86 were significantly decreased by high glucose concentrations compared with low glucose concentrations. Confocal microscopy was used to detect Rab 5 and Lamp-1, proteins involved in the kinetics of antigen processing as early markers, and Rab 7 and cathepsin D as late markers. We observed a delay in the dynamics of the acquisition of Rab 7 and cathepsin D in high glucose concentrations. Moreover, the kinetics of the formation <i>M. tuberculosis</i> peptide–MHC II complexes in MDMs was decreased under high glucose concentrations, reducing their capacity for T cell activation. These findings suggest that high glucose concentrations directly affect antigenic processing, and therefore antigenic presentation. |
| first_indexed | 2024-03-10T04:33:58Z |
| format | Article |
| id | doaj.art-b067ab7acb9249f2ab6aea0eed090517 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T04:33:58Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-b067ab7acb9249f2ab6aea0eed0905172023-11-23T03:58:46ZengMDPI AGBiomolecules2218-273X2021-11-011112176310.3390/biom11121763High Glucose Concentrations Impair the Processing and Presentation of <i>Mycobacterium tuberculosis</i> Antigens In VitroGuadalupe Monroy-Mérida0Silvia Guzmán-Beltrán1Fernando Hernández2Teresa Santos-Mendoza3Karen Bobadilla4Laboratory of Immunopharmacology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City 14080, MexicoDepartment of Microbiology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City 14080, MexicoResearch Department of Virology and Micology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City 14080, MexicoLaboratory of Immunopharmacology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City 14080, MexicoLaboratory of Immunopharmacology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City 14080, MexicoType 2 diabetes is an established risk factor for tuberculosis, but the underlying mechanisms are largely unknown. We established an in vitro model to analyze the effect of high glucose concentrations in antigen processing and presentation in antigen-presenting cells. Human monocyte-derived macrophages (MDMs) were exposed to high (11 mM and 30 mM) and low (5.5 mM) glucose concentrations and infected with <i>Mycobacterium tuberculosis (Mtb)</i>. Flow cytometry was used to analyze the effect of high glucose concentrations in histocompatibility complex (MHC) class II molecules (HLA-DR) and co-stimulatory molecules (CD80 and CD86), indispensable for an adequate antigenic presentation and CD4+ T cell activation. HLA-DR and CD86 were significantly decreased by high glucose concentrations compared with low glucose concentrations. Confocal microscopy was used to detect Rab 5 and Lamp-1, proteins involved in the kinetics of antigen processing as early markers, and Rab 7 and cathepsin D as late markers. We observed a delay in the dynamics of the acquisition of Rab 7 and cathepsin D in high glucose concentrations. Moreover, the kinetics of the formation <i>M. tuberculosis</i> peptide–MHC II complexes in MDMs was decreased under high glucose concentrations, reducing their capacity for T cell activation. These findings suggest that high glucose concentrations directly affect antigenic processing, and therefore antigenic presentation.https://www.mdpi.com/2218-273X/11/12/1763high glucose concentrationsmycobacterium tuberculosisantigenic processingantigenic presentationCD4+ T cells |
| spellingShingle | Guadalupe Monroy-Mérida Silvia Guzmán-Beltrán Fernando Hernández Teresa Santos-Mendoza Karen Bobadilla High Glucose Concentrations Impair the Processing and Presentation of <i>Mycobacterium tuberculosis</i> Antigens In Vitro Biomolecules high glucose concentrations mycobacterium tuberculosis antigenic processing antigenic presentation CD4+ T cells |
| title | High Glucose Concentrations Impair the Processing and Presentation of <i>Mycobacterium tuberculosis</i> Antigens In Vitro |
| title_full | High Glucose Concentrations Impair the Processing and Presentation of <i>Mycobacterium tuberculosis</i> Antigens In Vitro |
| title_fullStr | High Glucose Concentrations Impair the Processing and Presentation of <i>Mycobacterium tuberculosis</i> Antigens In Vitro |
| title_full_unstemmed | High Glucose Concentrations Impair the Processing and Presentation of <i>Mycobacterium tuberculosis</i> Antigens In Vitro |
| title_short | High Glucose Concentrations Impair the Processing and Presentation of <i>Mycobacterium tuberculosis</i> Antigens In Vitro |
| title_sort | high glucose concentrations impair the processing and presentation of i mycobacterium tuberculosis i antigens in vitro |
| topic | high glucose concentrations mycobacterium tuberculosis antigenic processing antigenic presentation CD4+ T cells |
| url | https://www.mdpi.com/2218-273X/11/12/1763 |
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