Evaluation of antifungal and anti-inflamatory activity of curcuminoids and chalconoids during co-culture of Trichophyton rubrum with THP-1 human macrophage cell line

Abstract

Trichophyton rubrum is the agent that induces 69.5% of superficial infections caused by dermatophytes. Currently there is an increase in infections caused by dermatophytes in immunosuppressed patients, in which these superficial infections present a more penetrating and invasive character, making it difficult to treat mycoses. Thus, the demand for new antifungal molecules is of importance due to the emergence of resistant strains of current therapy. The infectious process involves the initial contact of the dermatophyte with the host, which involves the adhesion process and the penetration of the tissue against the innate immune response of the host. Dermatophytes shows that circumvent the immune response of the host. However, studies aimed at clarifying the mechanisms of immune and inflammatory response against dermatophytoses are scarce, with a greater focus on other fungi of clinical interest. The production of reactive oxygen species (ROS) is involved in the inflammation process. Monitoring of ROS in the infectious process is of great importance, since the generation of these molecules by phagocytic cells (such as the macrophage) are essential in the defense mechanism of the host to combat infection. Thus, the objective of this project is to analyze the antifungal and anti-inflammatory activity of curcuminoids and chalconoides using the infection model of co-culture of T. rubrum with human macrophage (THP-1) cell line. The antifungal activity of the molecules will be evaluated by determining the minimum inhibitory concentration (MIC). The viability of cells infected with T. rubrum will be assessed by quantifying the release of the enzyme lactate dehydrogenase. The anti-inflammatory response of natural products during the co-culture will be assessed by quantifying pro-inflammatory cytokines (IL-2, IL-12, IL-17 and TNF-±) and the release of reactive oxygen species into the culture medium. In this way, we seek to evidence new natural compounds with anti-fungal and anti-inflammatory activity that may attenuate the process of invasive infection by dermatophytes in humans.