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TRICHODERMA STROMATICUM SPORES INDUCE AUTOPHAGY AND DOWNREGULATE INFLAMMATORY MEDIATORS IN HUMAN PERIPHERAL BLOOD-DERIVED MACROPHAGES
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Abstract
Trichoderma spp. are usually considered safe and normally used as biocontrol and biofertilization. Safety for
human health is evaluated by several tests that detect various effects such as allergenicity, toxicity, infectivity,
and pathogenicity. However, they do not evaluate the effects of the agent upon the immune system. The aim of
this study was to investigate the interaction between T. stromaticum spores and mammalian cells to assess the
immunomodulatory potential of the spores of this fungus. First, mouse macrophage cell line J774 and human
macrophages were exposed to fungal spores and analyzed for structural features, through scanning and transmission
electron microscopy. Then, various analysis were performed in human macrophages as to their effect in
some functional and molecular aspects of the immune system through immunocytochemistry, flow cytometry
and gene expression assays. We demonstrated that T. stromaticum spores induces autophagy and autophagyrelated
genes (ATGs) and downmodulate inflammatory mediators, including ROS, NLRP3, the cytokines IL-1β,
IL-18, IL-12 and IL-10, as well as TLR2, TLR4, miR-146b and miR-155, which may lead to an augmented susceptibility
to pathogens. Our study shows the extension of damages the biofungicide Tricovab® can cause in the
innate immune response. Further studies are necessary to elucidate other innate and adaptive immune responses
and, consequently, the safety of this fungus when in contact with humans.
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