Exposition to Biological Control Agent Trichoderma stromaticum Increases the Development of Cancer in Mice Injected With Murine Melanoma.

Biological control agents (BCA) are an alternative to chemical pesticides and an emerging strategy to safely eliminate plant pathogens. Trichoderma spp. are the most common fungi used as BCAs. They produce spores that are released into the air and can potentially interact with immune system of mammals. We previously showed that Trichoderma affects expression of genes encoding pattern recognition receptors (PRRs) and cytokines in mice. PRRs are involved in the recognition of microorganisms and can lead to pro-tumoral signaling. Here, we evaluated if mice injected with low doses of murine melanoma exhibited increased development of lung tumor when treated with conidia of T. stromaticum. Mice treated with T. stromaticum and inoculated with B16-F10 melanoma cells exhibited significant increase in tumor uptake (p = 0.006) and increased number of visible nodules in the lungs (p = 0.015). We also analyzed mRNA expression levels of genes encoding PRRs in lung of mice exposed to T. stromaticum and demonstrated that mice treated with T. stromaticum conidia exhibited lower expression levels of Clec7a and increased expression of Tlr4 (toll like receptor 4) compared to non-treated controls. The expression levels of Clec7a and Tlr2 were increased in mice treated with T. stromaticum and inoculated with murine melanoma compared to controls only inoculated with melanoma. Our results demonstrate that intranasal exposition to T. stromaticum increases tumor in the B16-F10 model, which may raise concerns regarding the safety of its use in agriculture.

17-ß-Estradiol increases macrophage activity through activation of the G-protein-coupled estrogen receptor and improves the response of female mice to Cryptococcus gattii.

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-ß-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.