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Published on: October 20, 2023
Cellular and Molecular Response of Macrophages THP-1 during Co-Culture with Inactive Trichophyton rubrum Conidia
Gabriela Gonzalez Segura1, Bruna Aline Cantelli1, Kamila Peronni2
1Biotechnology Unit, University of Ribeirão Preto-UNAERP, Av. Costábile Romano, 2201, Ribeirão Preto CEP 14096-900, São Paulo, Brazil.
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.
Insights
This study reveals how macrophages defend against Trichophyton rubrum by releasing inflammatory signals and altering microRNA expression. These findings shed light on the complex immune response to fungal infections.
Area of Science:
- Immunology
- Mycology
- Molecular Biology
Background:
- Trichophyton rubrum is increasingly implicated in invasive infections, particularly in immunocompromised and diabetic individuals.
- The intricate cellular and molecular mechanisms of fungal-host interactions remain incompletely understood.
Purpose of the Study:
- To elucidate the cellular and molecular interactions between human macrophages and Trichophyton rubrum.
- To investigate the role of microRNA modulation in the macrophage response to T. rubrum.
Main Methods:
- Co-culture of human macrophage cell line THP-1 with heat-inactivated T. rubrum conidia.
- Measurement of cytokine release (IL-6, IL-2), nuclear factor kappa beta (NF-κB) activation, and reactive oxygen species (ROS) production.
- Analysis of macrophage microRNA expression profiles using bioinformatics and qRT-PCR validation.
Main Results:
- Macrophage interaction with T. rubrum induced significant release of IL-6, IL-2, NF-κB, and increased ROS production.
- Co-culture resulted in the modulation of 83 microRNAs, with 33 repressed and 50 induced.
- In silico analysis indicated that target genes of modulated microRNAs are involved in inflammatory response, oxidative stress, apoptosis, and drug resistance.
Conclusions:
- Macrophages mount a defense against T. rubrum through inflammatory signaling and ROS production.
- T. rubrum infection significantly alters macrophage microRNA expression, impacting pathways crucial for immune response.
- Understanding these microRNA-mediated mechanisms offers potential targets for managing invasive T. rubrum infections.

