Role and mechanism of the Dectin‑1‑mediated Syk/NF‑κB signaling pathway in <em>Talaromyces marneffei</em> infection

Peng,Yang; Chen,Yan; Ma,Jinhong; Zhou,Wei; Wang,Yangyang; Wang,Yuyue; Zheng,Hui; Shi,Weifeng

doi:10.3892/etm.2021.11007

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

Authors:
- Yang Peng
- Yan Chen
- Jinhong Ma
- Wei Zhou
- Yangyang Wang
- Yuyue Wang
- Hui Zheng
- Weifeng Shi
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Affiliations: Department of Clinical Laboratory, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu 215000, P.R. China
Published online on: November 25, 2021 https://doi.org/10.3892/etm.2021.11007
Article Number: 84
Copyright: © Peng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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