HIV Progression Perturbs the Balance of the Cell-Mediated and Anti-Inflammatory Adaptive and Innate Mycobacterial Immune Response
Introduction. Our objective is to understand how HIV infection increases the risk of progression from latent tuberculosis (TB) to active disease. We understand now that immunity is a balance of competing immune responses by multiple cell types. Since T-lymphocyte production of interferon-gamma (IFN-...
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Wiley
2016-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2016/1478340 |
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| author | Andrew R. DiNardo Anna M. Mandalakas Gugu Maphalala Godwin Mtetwa Temhlanga Mndzebele Piluca Ustero Makhosazana Hlatshwayo Emily M. Mace Jordan S. Orange George Makedonas |
| author_facet | Andrew R. DiNardo Anna M. Mandalakas Gugu Maphalala Godwin Mtetwa Temhlanga Mndzebele Piluca Ustero Makhosazana Hlatshwayo Emily M. Mace Jordan S. Orange George Makedonas |
| author_sort | Andrew R. DiNardo |
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| description | Introduction. Our objective is to understand how HIV infection increases the risk of progression from latent tuberculosis (TB) to active disease. We understand now that immunity is a balance of competing immune responses by multiple cell types. Since T-lymphocyte production of interferon-gamma (IFN-γ) in response to Mycobacterium tuberculosis (Mtb) antigens fails to differentiate disease from latent infection, we applied a comprehensive profiling methodology to define immune biomarkers that reliably predict a patient’s TB risk. Methods. We established a cohort of HIV-infected adults with TB disease from Swaziland. Multiparametric flow cytometry was used to quantify the mycobacterial-specific anti-inflammatory (IL-4 and IL-10) and proinflammatory (IFN-γ) immune response. Results. From 12 HIV-infected Swaziland patients with TB disease, the CD4+, CD8+, Double Negative, and CD56+CD3− lymphocytes increase their IL-4 : IFN-γ ratio as HIV disease worsens (Spearman r of −0.59; −0.59; −0.60; and −0.59, resp.; p<0.05). Similarly, HIV severity is associated with an increased IL-10 : IFN-γ ratio (Spearman r of −0.76; p=0.01). Conclusion. As HIV disease progresses, both the adaptive and innate branches skew away from an inflammatory and towards anti-inflammatory phenotype. |
| format | Article |
| id | doaj-art-715aaa7838084f958f39a24931d2a45b |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-715aaa7838084f958f39a24931d2a45b2025-02-03T05:51:58ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/14783401478340HIV Progression Perturbs the Balance of the Cell-Mediated and Anti-Inflammatory Adaptive and Innate Mycobacterial Immune ResponseAndrew R. DiNardo0Anna M. Mandalakas1Gugu Maphalala2Godwin Mtetwa3Temhlanga Mndzebele4Piluca Ustero5Makhosazana Hlatshwayo6Emily M. Mace7Jordan S. Orange8George Makedonas9The Global Tuberculosis Program, Texas Children’s Hospital, Immigrant and Global Health, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USAThe Global Tuberculosis Program, Texas Children’s Hospital, Immigrant and Global Health, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USANational Tuberculosis Reference Laboratory, Swaziland Health Laboratory Services, Ministry of Health, Mbabane, SwazilandThe Global Tuberculosis Program, Texas Children’s Hospital, Baylor College of Medicine Children’s Foundation-Swaziland, Mbabane, SwazilandThe Global Tuberculosis Program, Texas Children’s Hospital, Baylor College of Medicine Children’s Foundation-Swaziland, Mbabane, SwazilandThe Global Tuberculosis Program, Texas Children’s Hospital, Baylor College of Medicine Children’s Foundation-Swaziland, Mbabane, SwazilandThe Global Tuberculosis Program, Texas Children’s Hospital, Baylor College of Medicine Children’s Foundation-Swaziland, Mbabane, SwazilandDepartment of Pathology and Immunology, Baylor College of Medicine, Texas Children’s Hospital Center for Human Immunobiology, Department of Pediatrics, Houston, TX 77030, USADepartment of Pathology and Immunology, Baylor College of Medicine, Texas Children’s Hospital Center for Human Immunobiology, Department of Pediatrics, Houston, TX 77030, USADepartment of Pathology and Immunology, Baylor College of Medicine, Texas Children’s Hospital Center for Human Immunobiology, Department of Pediatrics, Houston, TX 77030, USAIntroduction. Our objective is to understand how HIV infection increases the risk of progression from latent tuberculosis (TB) to active disease. We understand now that immunity is a balance of competing immune responses by multiple cell types. Since T-lymphocyte production of interferon-gamma (IFN-γ) in response to Mycobacterium tuberculosis (Mtb) antigens fails to differentiate disease from latent infection, we applied a comprehensive profiling methodology to define immune biomarkers that reliably predict a patient’s TB risk. Methods. We established a cohort of HIV-infected adults with TB disease from Swaziland. Multiparametric flow cytometry was used to quantify the mycobacterial-specific anti-inflammatory (IL-4 and IL-10) and proinflammatory (IFN-γ) immune response. Results. From 12 HIV-infected Swaziland patients with TB disease, the CD4+, CD8+, Double Negative, and CD56+CD3− lymphocytes increase their IL-4 : IFN-γ ratio as HIV disease worsens (Spearman r of −0.59; −0.59; −0.60; and −0.59, resp.; p<0.05). Similarly, HIV severity is associated with an increased IL-10 : IFN-γ ratio (Spearman r of −0.76; p=0.01). Conclusion. As HIV disease progresses, both the adaptive and innate branches skew away from an inflammatory and towards anti-inflammatory phenotype.http://dx.doi.org/10.1155/2016/1478340 |
| spellingShingle | Andrew R. DiNardo Anna M. Mandalakas Gugu Maphalala Godwin Mtetwa Temhlanga Mndzebele Piluca Ustero Makhosazana Hlatshwayo Emily M. Mace Jordan S. Orange George Makedonas HIV Progression Perturbs the Balance of the Cell-Mediated and Anti-Inflammatory Adaptive and Innate Mycobacterial Immune Response Mediators of Inflammation |
| title | HIV Progression Perturbs the Balance of the Cell-Mediated and Anti-Inflammatory Adaptive and Innate Mycobacterial Immune Response |
| title_full | HIV Progression Perturbs the Balance of the Cell-Mediated and Anti-Inflammatory Adaptive and Innate Mycobacterial Immune Response |
| title_fullStr | HIV Progression Perturbs the Balance of the Cell-Mediated and Anti-Inflammatory Adaptive and Innate Mycobacterial Immune Response |
| title_full_unstemmed | HIV Progression Perturbs the Balance of the Cell-Mediated and Anti-Inflammatory Adaptive and Innate Mycobacterial Immune Response |
| title_short | HIV Progression Perturbs the Balance of the Cell-Mediated and Anti-Inflammatory Adaptive and Innate Mycobacterial Immune Response |
| title_sort | hiv progression perturbs the balance of the cell mediated and anti inflammatory adaptive and innate mycobacterial immune response |
| url | http://dx.doi.org/10.1155/2016/1478340 |
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