Dynamics of adrenal steroids are related to variations in Th1 and Treg populations during Mycobacterium tuberculosis infection in HIV positive persons

• Published in: PloS one Vol. 7; no. 3; p. e33061
• Main Authors: Quiroga, Maria Florencia, Angerami, Matias Tomas, Santucci, Natalia, Ameri, Diego, Francos, Jose Luis, Wallach, Jorge, Sued, Omar, Cahn, Pedro, Salomón, Horacio, Bottasso, Oscar
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14-03-2012; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adrenal Glands - drug effects; Adrenal Glands - metabolism; Adult; AIDS; Antiretroviral agents; Antiviral agents; Biology; CD25 antigen; CD4 antigen; Cell number; Coinfection - blood; Coinfection - complications; Coinfection - immunology; Comparative analysis; Correlation; Data processing; Dehydroepiandrosterone; Dehydroepiandrosterone - pharmacology; Dehydroepiandrosterone sulfate; Female; Forkhead Transcription Factors - metabolism; Foxp3 protein; Glucocorticoids; Health aspects; Helper cells; Highly active antiretroviral therapy; HIV; HIV Infections - blood; HIV Infections - complications; HIV Infections - immunology; HIV Infections - microbiology; HIV patients; Human immunodeficiency virus; Humans; Hydrocortisone; Immune reconstitution; Immune Reconstitution Inflammatory Syndrome - blood; Immune Reconstitution Inflammatory Syndrome - complications; Immune Reconstitution Inflammatory Syndrome - immunology; Immune response; Immune system; Infection; Infections; Inflammation; Interferon-gamma - immunology; Interleukin-2 Receptor alpha Subunit - metabolism; Lupus; Lymphocytes T; Male; Medicine; Middle Aged; Mycobacterium; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - physiology; Patients; Peripheral blood mononuclear cells; Plasma levels; Populations; Sex hormones; Steroid hormones; Steroids; Steroids - blood; Steroids - metabolism; Sulfate; Sulfates; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - microbiology; Th1 Cells - drug effects; Th1 Cells - immunology; Tuberculosis; Tuberculosis - blood; Tuberculosis - complications; Tuberculosis - immunology; Argentina
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0033061

Tuberculosis (TB) remains the most frequent cause of illness and death from an infectious agent, and its interaction with HIV has devastating effects. We determined plasma levels of dehydroepiandrosterone (DHEA), its circulating form DHEA-suphate (DHEA-s) and cortisol in different stages of M. tuberculosis infection, and explored their role on the Th1 and Treg populations during different scenarios of HIV-TB coinfection, including the immune reconstitution inflammatory syndrome (IRIS), a condition related to antiretroviral treatment. DHEA levels were diminished in HIV-TB and HIV-TB IRIS patients compared to healthy donors (HD), HIV+ individuals and HIV+ individuals with latent TB (HIV-LTB), whereas dehydroepiandrosterone sulfate (DHEA-s) levels were markedly diminished in HIV-TB IRIS individuals. HIV-TB and IRIS patients presented a cortisol/DHEA ratio significantly higher than HIV+, HIV-LTB and HD individuals. A positive correlation was observed between DHEA-s and CD4 count among HIV-TB individuals. Conversely, cortisol plasma level inversely correlated with CD4 count within HIV-TB individuals. M. tuberculosis-specific Th1 lymphocyte count was increased after culturing PBMC from HIV-TB individuals in presence of DHEA. We observed an inverse correlation between DHEA-s plasma level and Treg frequency in co-infected individuals, and CD4+FoxP3+ Treg frequency was increased in HIV-TB and IRIS patients compared to other groups. Strikingly, we observed a prominent CD4+CD25-FoxP3+ population across HIV-TB and HIV-TB IRIS patients, which frequency correlated with DHEA plasma level. Finally, DHEA treatment negatively regulated FoxP3 expression without altering Treg frequency in co-infected patients. These data suggest an enhancing role for DHEA in the immune response against M. tuberculosis during HIV-TB coinfection and IRIS.