title: HIV Progression Perturbs the Balance of the Cell-Mediated and Anti-Inflammatory Adaptive and Innate Mycobacterial Immune Response.
abstract: BACKGROUND
  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).
  
  
  CONCLUSIONS
  As HIV disease progresses, both the adaptive and innate branches skew away from an inflammatory and towards anti-inflammatory phenotype.
authors.affiliation: The Global Tuberculosis Program, Texas Children's Hospital, Immigrant and Global Health, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: DiNardo
authors.affiliation: The Global Tuberculosis Program, Texas Children's Hospital, Immigrant and Global Health, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Mandalakas
authors.affiliation: National Tuberculosis Reference Laboratory, Swaziland Health Laboratory Services, Ministry of Health, Mbabane, Swaziland.
authors.forename: Gugu
authors.initials: G
authors.lastname: Maphalala
authors.affiliation: The Global Tuberculosis Program, Texas Children's Hospital, Baylor College of Medicine Children's Foundation-Swaziland, Mbabane, Swaziland.
authors.forename: Godwin
authors.initials: G
authors.lastname: Mtetwa
authors.affiliation: The Global Tuberculosis Program, Texas Children's Hospital, Baylor College of Medicine Children's Foundation-Swaziland, Mbabane, Swaziland.
authors.forename: Temhlanga
authors.initials: T
authors.lastname: Mndzebele
authors.affiliation: The Global Tuberculosis Program, Texas Children's Hospital, Baylor College of Medicine Children's Foundation-Swaziland, Mbabane, Swaziland.
authors.forename: Piluca
authors.initials: P
authors.lastname: Ustero
authors.affiliation: The Global Tuberculosis Program, Texas Children's Hospital, Baylor College of Medicine Children's Foundation-Swaziland, Mbabane, Swaziland.
authors.forename: Makhosazana
authors.initials: M
authors.lastname: Hlatshwayo
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Texas Children's Hospital Center for Human Immunobiology, Department of Pediatrics, Houston, TX 77030, USA.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Mace
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Texas Children's Hospital Center for Human Immunobiology, Department of Pediatrics, Houston, TX 77030, USA.
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Orange
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Texas Children's Hospital Center for Human Immunobiology, Department of Pediatrics, Houston, TX 77030, USA.
authors.forename: George
authors.initials: G
authors.lastname: Makedonas
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics / Q000502:physiology*; D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000502:physiology*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D017252:CD3 Complex; D019002:CD56 Antigen; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma