Petrucelli Monise Fazolin, Cantelli Bruna Aline M, Marins Mozart, Fachin Ana Lúcia
Biotechnology Unity, University of Ribeirão Preto (UNAERP), Ribeirao Preto 14096-900, Brazil.
Laboratory of Genetics and Molecular Biology of Fungi, Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto 14049-900, Brazil.
J Fungi (Basel). 2022 Oct 31;8(11):1151. doi: 10.3390/jof8111151.
is the most causative agent of dermatophytosis worldwide. The keratinocytes are the first line of defense during infection, triggering immunomodulatory responses. Previous dual RNA-seq data showed the upregulation of several human genes involved in immune response and epithelial barrier integrity during the co-culture of HaCat cells with . This work evaluates the transcriptional response of this set of genes during the co-culture of HaCat with different stages of conidia development and viability. Our results show that the developmental stage of fungal conidia and their viability interfere with the transcriptional regulation of innate immunity genes. The gene encoding the cytokine GM-CSF is the most overexpressed, and we report for the first time that expression is contact and conidial-viability-dependent during infection. In contrast, transcripts and GM-CSF secretion levels were observed when HaCat cells were challenged with bacterial LPS. Furthermore, the secretion of proinflammatory cytokines was dependent on the conidia developmental stage. Thus, we suggest that the viability and developmental stage of fungal conidia interfere with the transcriptional patterns of genes encoding immunomodulatory proteins in human keratinocytes with regard to important roles of GM-CSF during infection.
是全球皮肤癣菌病最主要的致病因子。角质形成细胞是感染期间的第一道防线,可触发免疫调节反应。先前的双RNA测序数据显示,在HaCat细胞与……共培养期间,参与免疫反应和上皮屏障完整性的几个人类基因上调。这项工作评估了在HaCat与不同发育阶段和活力的分生孢子共培养期间这组基因的转录反应。我们的结果表明,真菌分生孢子的发育阶段及其活力会干扰先天免疫基因的转录调控。编码细胞因子GM-CSF的基因表达上调最为明显,并且我们首次报道在感染期间其表达依赖于接触和分生孢子活力。相反,当HaCat细胞受到细菌LPS刺激时,观察到……转录本和GM-CSF分泌水平。此外,促炎细胞因子的分泌取决于分生孢子的发育阶段。因此,鉴于GM-CSF在感染期间的重要作用,我们认为真菌分生孢子的活力和发育阶段会干扰人类角质形成细胞中编码免疫调节蛋白的基因的转录模式。