The Influence of sex steroid hormones in the immunopathology of experimental pulmonary tuberculosis

BINI E; MATA ESPINOSA D; MARQUINA CASTILLO B; BARRIOS PAYAN J; COLUCCI D; CRUZ AF; ZATARAIN ZL; ALFONSECA ; ROMANO M; BOTTASSO O; HERNANDEZ PANDO R

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2014 vol. 9 p. 93831 - 93838

1932-6203

In most developing countries there are twice as many cases of tuberculosis (TB) reported among men than among women, a difference commonly attributed to biological and epidemiological factors. Since the biological perspective, steroid sex hormones such as androgens and estrogens can be a significant factor for this gender difference. Testosterone impairs macrophage activation and promotes the production of Th-2 cytokines, while estrogens are considered as pro-inflammatory mediators. The aim of this work was to compare the evolution of pulmonary tuberculosis in male and female mice using a well characterized model of progressive pulmonary tuberculosis. Groups of BALB/c mice, eight week age, of both genders were randomized into two groups: castrated or sham-operated. Two weeks later, animals were infected by the intratracheal route with a high dose of Mycobacterium tuberculosis strain H37Rv. Mice were euthanized at different time points and their lungs were used to determine bacilli loads (colony-forming units), inflammation in alveolar-capillary interstitium, perivenular and peribronchiolar areas, granuloma size and pneumonia extension (automated histo-morphometry), cytokine expression (real time PCR) and survival. Non-castrated male mice showed significant higher mortality and bacilli burdens during late disease than female animals. Female mice exhibited along the whole course of infection higher inflammation in all lung compartments, as well as the highest TNF-alpha expression and alveolar inflammation after one month of infection. Castrated male mice showed similar features than female non-castrated mice, while no significant differences were observed between castrated and non-castrated females. Thus, male mice are more susceptible to TB than females. This higher susceptibility was prevented by castration, suggesting that testosterone is a significant susceptibility factor, probably by its anti-inflammatory and cell-mediated immune suppressive effects.