P041
Dueling forces: how glucocorticoids both help and hurt in tuberculosis.
P Soldevilla(1,2,3,4,5) M Vidal(1,2,3,4) M Cortacans(1,2,3,4) E Fuentes(1,2,4) Y Rosales(2) J Díaz(2) P J Cardona(1,2,3,4,5)
1:Unitat de Tuberculosi Experimental, Microbiology Dept. Germans Trias i Pujol Research Institute and Hospital (IGTP-HUGTIP), Badalona, 08916, Spain; 2:Centre de Medicina Comparativa i Bioimatge de Catalunya (CMCiB), Badalona, 08916, Spain; 3:Genetics and Microbiology Department, Autonomous University of Barcelona, Barcelona, 08193, Spain; 4:Servei de Microbiologia, LCMN, Hospital Universitari Germans Trias i Pujol (HUGTiP), Badalona, 08916, Spain; 5:Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, 28029, Spain
Tuberculosis (TB) remains one of the deadliest infectious diseases worldwide, causing 1.25 million deaths in 2023. Immune dysregulation is associated with poorer TB outcomes. Intriguingly TB rates are significantly higher in men than in women (with an x1.7 ratio). We investigated the role of stress-response glucocorticoids (GCs) and their intrinsic anti-inflammatory activity, focusing on the influence of age, sex, and psychological stress using the active TB mouse model C3HeB/FeJ.
Mice of different ages were infected intravenously with 2 × 10⁴ colony-forming units (CFUs) of Mycobacterium tuberculosis (Mtb), and infection was allowed to progress over four weeks. Hair, lung, and spleen samples were collected to measure corticosterone production and assess infection progression. In a parallel psychological stress experiment, mice were divided into 'Control' (no stress) and 'RST' (daily movement restriction) groups, following the same infection protocol. Weekly blood samples were collected for corticosterone quantification.
Elderly female mice exhibited the highest corticosterone levels. RST animals also showed elevated corticosterone, with females displaying higher levels than males. Elevated corticosterone was associated with reduced pulmonary damage, characterised by lower neutrophil infiltration, without affecting lung bacillary load but increasing bacterial dissemination to the spleen.
These findings suggest a dichotomous effect of GCs: reducing the extracellular bacillary population through dampened inflammatory responses while promoting intracellular bacillary survival by impairing Th1-mediated immunity. Further studies are in progress to explore the sex-specific impact of stress-induced GCs on TB outcomes.