PMID- 22431997 OWN - NLM STAT- MEDLINE DCOM- 20120713 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 7 IP - 3 DP - 2012 TI - Dynamics of adrenal steroids are related to variations in Th1 and Treg populations during Mycobacterium tuberculosis infection in HIV positive persons. PG - e33061 LID - 10.1371/journal.pone.0033061 [doi] LID - e33061 AB - 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. FAU - Quiroga, Maria Florencia AU - Quiroga MF AD - Department of Microbiology, National Reference Center for AIDS, University of Buenos Aires School of Medicine, Buenos Aires, Argentina. fquiroga@fmed.uba.ar FAU - Angerami, Matias Tomas AU - Angerami MT FAU - Santucci, Natalia AU - Santucci N FAU - Ameri, Diego AU - Ameri D FAU - Francos, Jose Luis AU - Francos JL FAU - Wallach, Jorge AU - Wallach J FAU - Sued, Omar AU - Sued O FAU - Cahn, Pedro AU - Cahn P FAU - Salomon, Horacio AU - Salomon H FAU - Bottasso, Oscar AU - Bottasso O LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120314 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (FOXP3 protein, human) RN - 0 (Forkhead Transcription Factors) RN - 0 (Interleukin-2 Receptor alpha Subunit) RN - 0 (Steroids) RN - 459AG36T1B (Dehydroepiandrosterone) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Adrenal Glands/drug effects/*metabolism MH - Adult MH - Coinfection/blood/complications/immunology MH - Dehydroepiandrosterone/pharmacology MH - Female MH - Forkhead Transcription Factors/metabolism MH - HIV Infections/blood/complications/*immunology/microbiology MH - Humans MH - Immune Reconstitution Inflammatory Syndrome/blood/complications/immunology MH - Interferon-gamma/immunology MH - Interleukin-2 Receptor alpha Subunit/metabolism MH - Male MH - Middle Aged MH - Mycobacterium tuberculosis/drug effects/*physiology MH - Steroids/blood/*metabolism MH - T-Lymphocytes, Regulatory/drug effects/*microbiology MH - Th1 Cells/drug effects/*immunology MH - Tuberculosis/blood/complications/*immunology PMC - PMC3303789 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2012/03/21 06:00 MHDA- 2012/07/14 06:00 PMCR- 2012/03/14 CRDT- 2012/03/21 06:00 PHST- 2011/11/17 00:00 [received] PHST- 2012/02/03 00:00 [accepted] PHST- 2012/03/21 06:00 [entrez] PHST- 2012/03/21 06:00 [pubmed] PHST- 2012/07/14 06:00 [medline] PHST- 2012/03/14 00:00 [pmc-release] AID - PONE-D-11-23005 [pii] AID - 10.1371/journal.pone.0033061 [doi] PST - ppublish SO - PLoS One. 2012;7(3):e33061. doi: 10.1371/journal.pone.0033061. Epub 2012 Mar 14.