Immune Activation at Sites of HIV/TB Co-Infection Contributes to the Pathogenesis of HIV-1 Disease

• Published in: PloS one 2016-11, Vol.11 (11), p.e0166954-e0166954
• Main Authors: Meng, Qinglai, Sayin, Ismail, Canaday, David H, Mayanja-Kizza, Harriet, Baseke, Joy, Toossi, Zahra
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antigens, CD - immunology; Antiretroviral drugs; Biology and Life Sciences; Blood; CCR5 protein; CD38 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; CD69 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; Cell activation; Coinfection - immunology; Effector cells; Fatty acid-binding protein; Fatty acids; Female; Health aspects; Histocompatibility antigen HLA; HIV; HIV Infections - immunology; HIV Infections - microbiology; HIV Infections - pathology; HIV-1 - immunology; HLA-DR Antigens - immunology; Human immunodeficiency virus; Humans; Immunologic Memory; Immunological memory; Infection; Infections; Interleukin 1; Interleukin 1 receptor antagonist; Intestine; Lentivirus; Lymphocytes; Lymphocytes T; Macrophages; Male; Markers; Medical research; Medicine and Health Sciences; Memory cells; Middle Aged; Mortality; Mycobacterium tuberculosis - immunology; Pathogenesis; Patients; Peripheral blood mononuclear cells; Phenotypes; Pleural fluid; Protein binding; Retroviridae; T cell receptors; T cells; Tuberculosis; Tuberculosis, Pulmonary - immunology; Tuberculosis, Pulmonary - pathology; Tuberculosis, Pulmonary - virology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0166954

Systemic immune activation is critical to the pathogenesis of HIV-1 disease, and is accentuated in HIV/TB co-infected patients. The contribution of immune activation at sites of HIV/TB co-infection to viral activity, CD4 T cell count, and productive HIV-1 infection remain unclear. In this study, we measured markers of immune activation both in pleural fluid and plasma, and in T cells in pleural fluid mononuclear cell (PFMC) and peripheral blood mononuclear cell (PBMC) in HIV/TB co-infected subjects. The relationship between soluble and T cell activation markers with viral load in pleural fluid and blood CD4 T cell count were assessed. The T cell phenotype and activation status of HIV-1 p24 + T cells in PFMC and PBMC from HIV/TB patients were determined. We found that T cell and macrophage-specific and non-specific soluble markers of immune activation, sCD27, sCD163, IL1Ra, and sCD14, were higher in pleural fluid as compared to plasma from HIV/TB co-infected subjects, and higher as compared to pleural fluid from TB mono-infected subjects. Intestinal fatty acid-binding protein, a marker of intestinal tract damage, in plasma from HIV/TB co-infected patients was not different than that in HIV+ subjects. Expression of HLADR and CD38 double positive (HLADR/CD38) on CD4 T cells, and CD69+ on CD8 T cells correlated with pleural fluid viral load, and inversely with blood CD4 T cell count. Higher expression of HLADR/CD38 and CCR5 on CD4 T cells, and HLADR/CD38 and CD69 on CD8 T cells in PFMC were limited to effector memory populations. HIV-1 p24+ CD8 negative (includes CD4 + and double negative T cells) effector memory T cells in PFMC had higher expression of HLADR/CD38, Ki67, and CCR5 compared to HIV-1 p24- CD8 negative PFMC. Cumulatively, these data indicate that sites of HIV/TB co-infection are the source of intense immune activation.