AUTHOR=Santos Uener R. dos , Costa Marliete C. , de Freitas Gustavo J. C. , de Oliveira Flávia S. , Santos Bianca R. , Silva Juneo F. , Santos Daniel A. , Dias Adriana A. M. , de Carvalho Luciana D. , Augusto Danillo G. , dos Santos Jane L. 

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.00252

DOI=10.3389/fcimb.2020.00252

ISSN=2235-2988

ABSTRACT=<p>Biological control agents (BCA) are an alternative to chemical pesticides and an emerging strategy to safely eliminate plant pathogens. <italic>Trichoderma</italic> 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 <italic>Trichoderma</italic> 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 <italic>T. stromaticum</italic>. Mice treated with <italic>T. stromaticum</italic> and inoculated with B16-F10 melanoma cells exhibited significant increase in tumor uptake (<italic>p</italic> = 0.006) and increased number of visible nodules in the lungs (<italic>p</italic> = 0.015). We also analyzed mRNA expression levels of genes encoding PRRs in lung of mice exposed to <italic>T. stromaticum</italic> and demonstrated that mice treated with <italic>T. stromaticum</italic> conidia exhibited lower expression levels of <italic>Clec7a</italic> and increased expression of <italic>Tlr4</italic> (toll like receptor 4) compared to non-treated controls. The expression levels of <italic>Clec7a</italic> and <italic>Tlr2</italic> were increased in mice treated with <italic>T. stromaticum</italic> and inoculated with murine melanoma compared to controls only inoculated with melanoma. Our results demonstrate that intranasal exposition to <italic>T. stromaticum</italic> increases tumor in the B16-F10 model, which may raise concerns regarding the safety of its use in agriculture.</p>