Journal
CELLULAR MICROBIOLOGY
Volume 22, Issue 6, Pages -Publisher
WILEY
DOI: 10.1111/cmi.13179
Keywords
17-beta-estradiol; cryptococcosis; Cryptococcus gattii; GPER
Categories
Funding
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [403006/2016-3, 440010/2018-7, 302670/2017-3]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior
- Fundacao de Amparo a Pesquisa do Estado de Minas Gerais [APQ00727-16, PPM-00061-18]
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Cryptococcus gattii (Cg) is one of the agents of cryptococcosis, a severe systemic mycosis with a higher prevalence in men than women, but the influence of the female sex hormone, 17-beta-estradiol (E2), on cryptococcosis remains unclear. Our study shows that female mice presented delayed mortality, increased neutrophil recruitment in bronchoalveolar lavage fluid, and reduced fungal load after 24 hr of infection compared to male and ovariectomised female mice (OVX). E2 replacement restored OVX female survival. Female macrophages have more efficient fungicidal activity, which was increased by E2 and reversed by the antagonist of G-protein-coupled oestrogen receptor (GPER), which negatively modulates PI3K activation. Furthermore, E2 induces a reduction in Cg cell diameter, cell charge, and antioxidant peroxidase activity. In conclusion, female mice present improved control of Cg infection, and GPER is important for E2 modulation of the female response.
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