Effect of circulating and local levels of cortisol on gene expression in mononuclear cells from patients with pulmonary or pleural tuberculosis

GALLUCCI, GEORGINA; IMHOFF, MATILDE; DIAB, MAGDALENA; BONGIOVANNI, BETTINA; DIAZ, ARIANA; SANTUCCI, NATALIA; ESTEFANÍA, MASSA; BERTOLA, DIEGO; DERIO, MARISA; BOTTASSO, OSCAR; BAY, MARÍA LUISA; D ATTILIO, LUCIANO

Rosario

Jornada; XVI Jornadas de Ciencias, Tecnologías e Innovación; 2022

Universidad Nacional de Rosario

Tuberculosis (TB) constitutes one of the main global public health concerns. Its main manifestation is pulmonary TB (PTB), while pleural TB (PLTB) is the most common extrapulmonary form. Since the cellular immune response (IR) is essential for the containment and resolution of the pathology, PLTB is a natural model to study defensive mechanisms at the site of infection, and the ensuing endocrine response. We have previously shown that patients with PLTB have a greater inflammatory and cellular response in the pleural compartment (increased IL-1β, IL-6, and IFN-ɣtogether with low cortisol levels) as compared to the systemic compartment. The aim of this study was to analyze by RT-qPCR the transcription profile of genes regulated by the Glucocorticoid Receptor (GR), such as ANXA1, GILZ, FKBP5, NFKBIA, NFKBIB, IL1-β, IL-6, and IFNɣ, in peripheral blood mononuclear cells (PBMC) from patients with PTB and PLTB, as well as from healthy controls (Co). We also examined the expression of these genes in pleural exudate cells (PEMC) from PLTB patients. TB and PLTB patients displayed increased mRNA levels of ANXA1, GILZ, and NFKBIA compared to values determined in PEMC and in cells from Co. No between-group differencesin transcripts for FKBP5, NFkB1, and NFKBIB were observed. Within PTB patients, such increased expression was related to disease severity. mRNA levels of IL1-β were augmented in PBMC from PTB (vs. Co), whereas IL-6 and IFNɣtranscripts were elevated in PEMC (vs. PBMC). Collectively, PBMC from both groups of TB patients had an increased expression of GR-regulated anti-inflammatory genes with respect to Co and PEMC counterparts.