title: Dynamics of adrenal steroids are related to variations in Th1 and Treg populations during Mycobacterium tuberculosis infection in HIV positive persons.
abstract: 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.
authors.affiliation: Department of Microbiology, National Reference Center for AIDS, University of Buenos Aires School of Medicine, Buenos Aires, Argentina. fquiroga@fmed.uba.ar
authors.forename: Maria Florencia
authors.initials: MF
authors.lastname: Quiroga
authors.forename: Matias Tomas
authors.initials: MT
authors.lastname: Angerami
authors.forename: Natalia
authors.initials: N
authors.lastname: Santucci
authors.forename: Diego
authors.initials: D
authors.lastname: Ameri
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Francos
authors.forename: Jorge
authors.initials: J
authors.lastname: Wallach
authors.forename: Omar
authors.initials: O
authors.lastname: Sued
authors.forename: Pedro
authors.initials: P
authors.lastname: Cahn
authors.forename: Horacio
authors.initials: H
authors.lastname: Salomón
authors.forename: Oscar
authors.initials: O
authors.lastname: Bottasso
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D060085:Coinfection / Q000097:blood / Q000150:complications / Q000276:immunology; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000097:blood / Q000150:complications / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000502:physiology*; D013256:Steroids / Q000097:blood / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000382:microbiology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D014376:Tuberculosis / Q000097:blood / Q000150:complications / Q000276:immunology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D013256:Steroids; D003687:Dehydroepiandrosterone; D007371:Interferon-gamma