Cellular and Molecular Response of Macrophages THP-1 during Co-Culture with Inactive Trichophyton rubrum Conidia

Abstract

Trichophyton rubrum is causing an increasing number of invasive infections, especially in immunocompromised and diabetic patients. The fungal invasive infectious process is complex and has not yet been fully elucidated. Therefore, this study aimed to understand the cellular and molecular mechanisms during the interaction of macrophages and T. rubrum. For this purpose, we used a co-culture of previously germinated and heat-inactivated T. rubrum conidia placed in contact with human macrophages cell line THP-1 for 24 h. This interaction led to a higher level of release of interleukins IL-6, IL-2, nuclear factor kappa beta (NF-κB) and an increase in reactive oxygen species (ROS) production, demonstrating the cellular defense by macrophages against dead fungal elements. Cell viability assays showed that 70% of macrophages remained viable during co-culture. Human microRNA expression is involved in fungal infection and may modulate the immune response. Thus, the macrophage expression profile of microRNAs during co-culture revealed the modulation of 83 microRNAs, with repression of 33 microRNAs and induction of 50 microRNAs. These data were analyzed using bioinformatics analysis programs and the modulation of the expression of some microRNAs was validated by qRT-PCR. In silico analysis showed that the target genes of these microRNAs are related to the inflammatory response, oxidative stress, apoptosis, drug resistance, and cell proliferation.

Next-Generation Sequencing Applications for the Study of Fungal Pathogens

“…Moreover, Trichophyton rubrum is an opportunistic pathogen responsible for progressively expanding invasive diseases. NGS technology targeting microRNAs showed that the inactivated germinated T. rubrum microconidia co-cultured with human macrophages promoted the release of proinflammatory cytokines and changes in the regulation of microRNAs [ 31 ]. In addition, the group led by Ana Lúcia Fachin co-cultured T. rubrum CBS 118892 with human keratinocytes to assess the efficacy of terbinafine, a medicine used to treat dermatophyte infections [ 32 ].…”

Potential Treatment of Dermatophyte Trichophyton rubrum in Rat Model Using Topical Green Biosynthesized Silver Nanoparticles with Achillea santolina Extract

“…Other reports have described the morphological and ultrastructural modifications of T. rubrum hyphal cells that were treated with different antifungal agents. These include ME1111, which exerted its antifungal action through interfering with active transport system found in the cell membrane with subsequent cell lysis [ 60 ], and K101 nail solution, which disrupted the contact between the cell wall and the inner membrane [ 61 ].…”

Rosiglitazone alleviates lipopolysaccharide‑induced inflammation in RAW264.7 cells via inhibition of NF‑κB and in a PPARγ‑dependent manner

“…The aforementioned studies suggested that PPARγ could partly regulate the level of the NF-κB signaling pathway. NF-κB signaling pathway activation may be the control point for the expression of abundant inflammatory response genes ( 49 ). In the present study, rosiglitazone inhibited NF-κBp65 phosphorylation and increased IKBα expression, reversing LPS-induced activation of NF-κB.…”