Ting-Ting Wei1, Zhuo Cheng2, Zhi-De Hu3, Lin Zhou1, Ren-Qian Zhong1. 1. Department of Laboratory Medicine, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, China. 2. Department of Medical Oncology, Eastern Hepatobiliary Surgery Hospital/Institute, The Second Military Medical University, Shanghai 200438, China. 3. Department of Laboratory Medicine, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China.
Abstract
BACKGROUND: Candida albicans (C. albicans) is one of the most common fungal pathogens causing superficial and systemic infections. The innate immune system is the first defense line against C. albicans infection. MiR-155, a multifunctional microRNA (miRNA), has been proved to be a crucial regulator in innate immune response against bacterial and virus. However, the biological function of miR-155 in innate immune response against C. albicans infection remains unknown. METHODS: The expression miR-155, as well as inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)], in monocytes derived dendritic cells (DCs) during heat-killed C. albicans infection was detected by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). The biological functions of miR-155 were investigated with "gain- and loss-of-function" experiments. Potential targets of miR-155 were identified by bioinformatics analysis, luciferase assay and western blot. Small interfering RNA (siRNA) was used to validate the function of miR-155 target. RESULTS: C. albicans increased the expression of miR-155 and pro-inflammatory factors. MiR-155 induced by C. albicans was depended on Dectin-1-spleen tyrosine kinase (Syk)/Raf-1-MAPK signaling pathway. Furthermore, miR-155 suppressed the secretion of pro-inflammatory cytokines induced by C. albicans by targeting NF-κB p65 and B cell leukemia/lymphoma 10 (BCL-10). CONCLUSIONS: In conclusion, up-regulated miR-155 acts as a negative feedback regulator in the innate immune response against C. albicans infection. 2019 Annals of Translational Medicine. All rights reserved.
BACKGROUND: Candida albicans (C. albicans) is one of the most common fungal pathogens causing superficial and systemic infections. The innate immune system is the first defense line against C. albicans infection. MiR-155, a multifunctional microRNA (miRNA), has been proved to be a crucial regulator in innate immune response against bacterial and virus. However, the biological function of miR-155 in innate immune response against C. albicans infection remains unknown. METHODS: The expression miR-155, as well as inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)], in monocytes derived dendritic cells (DCs) during heat-killed C. albicans infection was detected by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). The biological functions of miR-155 were investigated with "gain- and loss-of-function" experiments. Potential targets of miR-155 were identified by bioinformatics analysis, luciferase assay and western blot. Small interfering RNA (siRNA) was used to validate the function of miR-155 target. RESULTS: C. albicans increased the expression of miR-155 and pro-inflammatory factors. MiR-155 induced by C. albicans was depended on Dectin-1-spleen tyrosine kinase (Syk)/Raf-1-MAPK signaling pathway. Furthermore, miR-155 suppressed the secretion of pro-inflammatory cytokines induced by C. albicans by targeting NF-κB p65 and B cell leukemia/lymphoma 10 (BCL-10). CONCLUSIONS: In conclusion, up-regulated miR-155 acts as a negative feedback regulator in the innate immune response against C. albicans infection. 2019 Annals of Translational Medicine. All rights reserved.
Authors: Katharina L Becker; Daniela C Ifrim; Jessica Quintin; Mihai G Netea; Frank L van de Veerdonk Journal: Semin Immunopathol Date: 2014-12-20 Impact factor: 9.623