Exposition of dermatophyte <i><scp>T</scp>richophyton mentagrophytes</i> to <scp>L</scp>‐cystine induces expression and activation of cysteine dioxygenase

Kašperová, Alena; Cahlikova, Romana; Kunert, J.; Šebela, Marek; Novák, Zdeněk; Raška, Milan

doi:10.1111/myc.12220

Cited by 8 publications

(2 citation statements)

References 37 publications

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“…To evaluate viability of the macrophage cell line during co-culture with T. rubrum LGC, the release of lactate dehydrogenase (LDH) was analyzed after different incubation periods (5,8,12,24, and 48 h) [29] using the TOX7 kit (Sigma-Aldrich) according to the manufacturer protocol, as described previously [20].…”

Section: Ldh Assay For Assessing the Viability Of Thp-1 Macrophages C...mentioning

confidence: 99%

“…Infection begins with fungal adherence, followed by the formation of hyphae that can spread through the tissue, releasing fungal enzymes and other pathogenic factors that mobilize keratinocytes, destroy the epidermal barrier, and increase fungal proliferation. These events trigger activation of the host's immune response [8], including the modulation of genes involved in the response to fungal infection, in the release of fungal virulence factors, and in the induction of inflammatory cascades [9].…”

Section: Introductionmentioning

confidence: 99%

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Transcriptome Analysis of Co-Cultures of THP-1 Human Macrophages with Inactivated Germinated Trichophyton rubrum Conidia

Cantelli

Segura

Bitencourt

et al. 2023

JoF

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Although most mycoses are superficial, the dermatophyte Trichophyton rubrum can cause systemic infections in patients with a weakened immune system, resulting in serious and deep lesions. The aim of this study was to analyze the transcriptome of a human monocyte/macrophage cell line (THP-1) co-cultured with inactivated germinated T. rubrum conidia (IGC) in order to characterize deep infection. Analysis of macrophage viability by lactate dehydrogenase quantification showed the activation of the immune system after 24 h of contact with live germinated T. rubrum conidia (LGC). After standardization of the co-culture conditions, the release of the interleukins TNF-α, IL-8, and IL-12 was quantified. The greater release of IL-12 was observed during co-culturing of THP-1 with IGC, while there was no change in the other cytokines. Next-generation sequencing of the response to T. rubrum IGC identified the modulation of 83 genes; of these, 65 were induced and 18 were repressed. The categorization of the modulated genes showed their involvement in signal transduction, cell communication, and immune response pathways. In total, 16 genes were selected for validation and Pearson’s correlation coefficient was 0.98, indicating a high correlation between RNA-seq and qPCR. Modulation of the expression of all genes was similar for LGC and IGC co-culture; however, the fold-change values were higher for LGC. Due to the high expression of the IL-32 gene in RNA-seq, we quantified this interleukin and observed an increased release in co-culture with T. rubrum. In conclusion, the macrophages-T. rubrum co-culture model revealed the ability of these cells to modulate the immune response, as demonstrated by the release of proinflammatory cytokines and the RNA-seq gene expression profile. The results obtained permit to identify possible molecular targets that are modulated in macrophages and that could be explored in antifungal therapies involving the activation of the immune system.

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Section: Ldh Assay For Assessing the Viability Of Thp-1 Macrophages C...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transcriptome Analysis of Co-Cultures of THP-1 Human Macrophages with Inactivated Germinated Trichophyton rubrum Conidia

Cantelli

Segura

Bitencourt

et al. 2023

JoF

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Mammalian Cysteine Dioxygenase

Driggers

Stipanuk

Karplus

2015

Encyclopedia of Inorganic and Bioinorganic Chemistry

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Cysteine dioxygenase (CDO) is a mononuclear nonheme Fe(II) enzyme that catalyzes the oxidation of l ‐cysteine to l ‐cysteinesulfinic acid (CSA) by addition of both atoms of molecular oxygen to the cysteine sulfur. Mammalian CDO is highly expressed in the liver, the pancreas, the adipose tissue, the kidney and the lungs, and the CSA produced is further converted to either taurine or sulfate plus pyruvate. To maintain cysteine levels within the narrow range required for health, mammalian CDO is regulated by the modulation of enzyme turnover and through formation of a Cys93‐Tyr157 crosslink that increases its activity over 10‐fold. Imbalances in cysteine metabolism have been observed in several neurological disorders, and CDO has been identified as a tumor suppressor. Bacterial CDOs also exist, as do a variety of related thiol dioxygenases that have been less well studied. High‐resolution crystal structures of CDO reveal iron coordination by three histidines. Cysteine coordinates the iron by its amino and thiolate groups, leaving a sixth coordination site open for dioxygen. A cysteine persulfenate has been trapped in the active site, but despite substantial spectroscopic studies and theoretical calculations, the details of the mechanism are still a matter of debate and it is uncertain if this is an intermediate.

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Pathogenesis of Dermatophytosis: Sensing the Host Tissue

2016

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The genera Trichophyton, Microsporum, and Epidermophyton include filamentous fungi that cause dermatophytosis, a superficial infection of the skin, stratum corneum, nail beds, and hair follicles. The ability of dermatophytes to adhere to these substrates and adapt to the host environment is essential for the establishment of infection. Several fungal enzymes and proteins participate in this adaptive response to the environment and to keratin degradation. Transcription factors such as PacC and Hfs1, as well as heat shock proteins, are involved in sensing and adapting to the acidic pH of the skin in the early stages of fungal-host interaction. During dermatophyte growth, with keratin as the sole carbon source, the extracellular pH shifts from acidic to alkaline. This creates an environment in which most of the known keratinolytic proteases exhibit optimal activity. These events culminate in the establishment and maintenance of the infection, which can be chronic or acute depending on the dermatophyte species. This review focuses on these and other molecular aspects of the dermatophyte-host interaction.

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Exposition of dermatophyte Trichophyton mentagrophytes to L‐cystine induces expression and activation of cysteine dioxygenase

Cited by 8 publications

References 37 publications

Transcriptome Analysis of Co-Cultures of THP-1 Human Macrophages with Inactivated Germinated Trichophyton rubrum Conidia

Transcriptome Analysis of Co-Cultures of THP-1 Human Macrophages with Inactivated Germinated Trichophyton rubrum Conidia

Mammalian Cysteine Dioxygenase

Pathogenesis of Dermatophytosis: Sensing the Host Tissue

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