Latent tuberculosis coinfection in mild COVID-19 is associated with a distinct immune cell phenotype marked by enhanced cytotoxic degranulation and mitochondrial alterations
IntroductionThe chronic nature of latent tuberculosis infection (LTBI) allows it to coexist with diverse pathologies. However, it remains unclear whether immune alterations associated with LTBI influence COVID-19 coinfection and patient outcomes. This study aims to compare the immune phenotype of pa...
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Frontiers Media S.A.
2025-05-01
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| author | Carlos Peña-Bates Lucero A. Ramón-Luing Julio Flores-Gonzalez Enrique Espinosa María F. Martinez-Moreno Karen Medina-Quero Marco A. Vargas-Hernandez Norma A. Téllez-Navarrete Fernando M. Sosa-Gomez Eduardo Becerril-Vargas Miguel Ángel Salazar Leslie Chavez-Galan |
| author_facet | Carlos Peña-Bates Lucero A. Ramón-Luing Julio Flores-Gonzalez Enrique Espinosa María F. Martinez-Moreno Karen Medina-Quero Marco A. Vargas-Hernandez Norma A. Téllez-Navarrete Fernando M. Sosa-Gomez Eduardo Becerril-Vargas Miguel Ángel Salazar Leslie Chavez-Galan |
| author_sort | Carlos Peña-Bates |
| collection | DOAJ |
| description | IntroductionThe chronic nature of latent tuberculosis infection (LTBI) allows it to coexist with diverse pathologies. However, it remains unclear whether immune alterations associated with LTBI influence COVID-19 coinfection and patient outcomes. This study aims to compare the immune phenotype of patients with LTBI/COVID-19 to those with COVID-19 alone, in order to assess whether latent tuberculosis infection induces significant immune cell alterations.MethodsPeripheral blood mononuclear cells were cultured and stimulated with the SARS-CoV-2 Spike protein and Mycobacterium bovis Bacillus Calmette-Guérin (M. bovis BCG) to evaluate cellular distribution and function.Resultsthe LTBI/COVID-19 group exhibited a narrower range of symptoms and required less complex treatment regimens than the COVID-19 group. The cellular evaluation revealed that individuals with COVID-19 displayed a distinct immune profile, characterized by a predominance of monocytes expressing pro-inflammatory and regulatory markers, including TNFR2, HLA-DR+TNFR2, and CD71. While CD4+ T cell subpopulation distribution and function were similar across groups, LTBI/COVID-19 and COVID-19 exhibited similar frequencies of CD8+perforin+ and CD8+Granzime B+ T cells. However, LTBI/COVID-19 displays lower soluble levels of granzyme B and perforin in culture supernatants and perforin, granulysin, and sFas in plasma compared to COVID-19. Notably, CD8+ T cells from LTBI/COVID-19 showed higher antigen-specific degranulation than COVID-19. Moreover, LTBI/COVID-19 individuals predominantly displayed CD4+ and CD8+ T cells with highly polarized, compact mitochondria at baseline, which remained unchanged under stimulation. In contrast, COVID-19 had T cells with highly polarized, fragmented mitochondria at baseline, a profile that persisted under stimulation.ConclusionThe findings reveal significant alterations in monocytes and T cells of individuals with LTBI/COVID-19, suggesting that co-infection may induce changes in the cellular phenotype and cytotoxic function of CD8 T cells. |
| format | Article |
| id | doaj-art-2a9ceea69bf344f788a345868d9c1e38 |
| institution | OA Journals |
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| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
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| spelling | doaj-art-2a9ceea69bf344f788a345868d9c1e382025-08-20T02:25:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15664491566449Latent tuberculosis coinfection in mild COVID-19 is associated with a distinct immune cell phenotype marked by enhanced cytotoxic degranulation and mitochondrial alterationsCarlos Peña-Bates0Lucero A. Ramón-Luing1Julio Flores-Gonzalez2Enrique Espinosa3María F. Martinez-Moreno4Karen Medina-Quero5Marco A. Vargas-Hernandez6Norma A. Téllez-Navarrete7Fernando M. Sosa-Gomez8Eduardo Becerril-Vargas9Miguel Ángel Salazar10Leslie Chavez-Galan11Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, MexicoLaboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, MexicoLaboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, MexicoLaboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, MexicoLaboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, MexicoLaboratory of Immunology, Escuela Militar de Graduados de Sanidad, Universidad del Ejército y Fuerza Aérea Mexicanos, Mexico City, MexicoLaboratory of Immunology, Escuela Militar de Graduados de Sanidad, Universidad del Ejército y Fuerza Aérea Mexicanos, Mexico City, MexicoDepartment of Healthcare Coordination, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, MexicoDepartment of Occupational and Preventive Health, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, MexicoLaboratory of Clinical Microbiology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, MexicoTuberculosis Clinic, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, MexicoLaboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, MexicoIntroductionThe chronic nature of latent tuberculosis infection (LTBI) allows it to coexist with diverse pathologies. However, it remains unclear whether immune alterations associated with LTBI influence COVID-19 coinfection and patient outcomes. This study aims to compare the immune phenotype of patients with LTBI/COVID-19 to those with COVID-19 alone, in order to assess whether latent tuberculosis infection induces significant immune cell alterations.MethodsPeripheral blood mononuclear cells were cultured and stimulated with the SARS-CoV-2 Spike protein and Mycobacterium bovis Bacillus Calmette-Guérin (M. bovis BCG) to evaluate cellular distribution and function.Resultsthe LTBI/COVID-19 group exhibited a narrower range of symptoms and required less complex treatment regimens than the COVID-19 group. The cellular evaluation revealed that individuals with COVID-19 displayed a distinct immune profile, characterized by a predominance of monocytes expressing pro-inflammatory and regulatory markers, including TNFR2, HLA-DR+TNFR2, and CD71. While CD4+ T cell subpopulation distribution and function were similar across groups, LTBI/COVID-19 and COVID-19 exhibited similar frequencies of CD8+perforin+ and CD8+Granzime B+ T cells. However, LTBI/COVID-19 displays lower soluble levels of granzyme B and perforin in culture supernatants and perforin, granulysin, and sFas in plasma compared to COVID-19. Notably, CD8+ T cells from LTBI/COVID-19 showed higher antigen-specific degranulation than COVID-19. Moreover, LTBI/COVID-19 individuals predominantly displayed CD4+ and CD8+ T cells with highly polarized, compact mitochondria at baseline, which remained unchanged under stimulation. In contrast, COVID-19 had T cells with highly polarized, fragmented mitochondria at baseline, a profile that persisted under stimulation.ConclusionThe findings reveal significant alterations in monocytes and T cells of individuals with LTBI/COVID-19, suggesting that co-infection may induce changes in the cellular phenotype and cytotoxic function of CD8 T cells.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1566449/fulllatent tuberculosisCOVID-19coinfectionT lymphocytesmitochondrial changes |
| spellingShingle | Carlos Peña-Bates Lucero A. Ramón-Luing Julio Flores-Gonzalez Enrique Espinosa María F. Martinez-Moreno Karen Medina-Quero Marco A. Vargas-Hernandez Norma A. Téllez-Navarrete Fernando M. Sosa-Gomez Eduardo Becerril-Vargas Miguel Ángel Salazar Leslie Chavez-Galan Latent tuberculosis coinfection in mild COVID-19 is associated with a distinct immune cell phenotype marked by enhanced cytotoxic degranulation and mitochondrial alterations Frontiers in Immunology latent tuberculosis COVID-19 coinfection T lymphocytes mitochondrial changes |
| title | Latent tuberculosis coinfection in mild COVID-19 is associated with a distinct immune cell phenotype marked by enhanced cytotoxic degranulation and mitochondrial alterations |
| title_full | Latent tuberculosis coinfection in mild COVID-19 is associated with a distinct immune cell phenotype marked by enhanced cytotoxic degranulation and mitochondrial alterations |
| title_fullStr | Latent tuberculosis coinfection in mild COVID-19 is associated with a distinct immune cell phenotype marked by enhanced cytotoxic degranulation and mitochondrial alterations |
| title_full_unstemmed | Latent tuberculosis coinfection in mild COVID-19 is associated with a distinct immune cell phenotype marked by enhanced cytotoxic degranulation and mitochondrial alterations |
| title_short | Latent tuberculosis coinfection in mild COVID-19 is associated with a distinct immune cell phenotype marked by enhanced cytotoxic degranulation and mitochondrial alterations |
| title_sort | latent tuberculosis coinfection in mild covid 19 is associated with a distinct immune cell phenotype marked by enhanced cytotoxic degranulation and mitochondrial alterations |
| topic | latent tuberculosis COVID-19 coinfection T lymphocytes mitochondrial changes |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1566449/full |
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