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

QUIROGA MF; ANGERAMI M; SANTUCCI N; AMERI D ; FRANCOS JL; WALLACH J; SUED; CAHN P; SALOMON H; BOTTASSO O

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: Boston; Año: 2012 vol. 7 p. 1 - 10

1932-6203

Tuberculosis (TB) remains the most frequent cause of illness and death from an infectious agent globally, and its interaction with HIV has devastating effects.  We have explored the role of adrenal hormones on the Th1 and Treg populations during different clinical scenarios of HIV-TB coinfection, including the immune reconstitution inflammatory syndrome (IRIS), a pro-inflammatory condition induced by antiretroviral treatment.  Dehydroepiandrosterone (DHEA) plasma levels were significantly diminished in HIV-TB and HIV-TB IRIS patients compared to healthy donors (HD),  HIV+ individuals and HIV+ individuals with latent TB infection (HIV+LTB), whereas dehydroepiandrosterone sulfate (DHEA-s) levels were markedly diminished in HIV-TB IRIS individuals. Coinfected patients 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.  In contrast, cortisol plasma level was inversely correlated with CD4 count within HIV-TB individuals.  In vitro assays showed that 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+FoxP3+CD25- 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 support a role for DHEA in the immune response against HIV and M. tuberculosis during HIV-TB coinfection and IRIS.