Alexandros G .Sfakianakis,ENT,Anapafeos 5 Agios Nikolaos Crete 72100 Greece,00302841026182

Κυριακή 26 Δεκεμβρίου 2021

Role and mechanism of the Dectin-1-mediated Syk/NF-κB signaling pathway in Talaromyces marneffei infection

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Exp Ther Med. 2022 Jan;23(1):84. doi: 10.3892/etm.2021.11007. Epub 2021 Nov 25.

ABSTRACT

Dendritic cell-associated C-type lectin-1 (Dectin-1), a C-type lectin receptor, serves a critical role in host antifungal immunity. However, the molecular mechanism and function of Dectin-1-mediated signaling in response to infection by the pathogenic fungus Talaromyces marneffei remains unclear. To understand the role of Dectin-1 signaling against T. marneffei infection, the phosphorylation of spleen tyrosine kinase (Syk), nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor, α (IκBα) and NF-κB were analyzed using western blotting, and the secretion of cytokines was detected using ELISA. Upon sporular or hyphal heat-killed T. marneffei stimulation, Dectin-1 in THP-1 macrophages recognized and induced the activation of Syk, and in turn triggered phosphorylation of downstream molecules IκBα and NF-κB, thus increasing the secretion of TNF-α and IL-8. Conversely, knockdown of Dectin-1 in THP-1 macrophages downregulated the phosphorylation of Syk, IκBα and NF-κB molecules, and significantly decreased the production of TNF-α and IL-8. These results indicated that Dectin-1 may have a crucial role in inducing the inflammatory response via increasing levels of TNF-α and IL-8 induced by T. marneffei, whereas NF-κB may be the key downstream molecule involved in the response to T. marneffei infection. Subsequently, THP-1 macrophages could orchestrate the innate immune system by releasing the cytokines TNF-α and IL-8. Therefore, it was hypothesized that regulation of the Dectin-1 signaling pathway may effectively interfere with the defense ability of the host against T. marneffei infection.

PMID:34938366 | PMC:PMC8688926 | DOI:10.3892/etm.2021.11007

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