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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. [ABSTRACT FROM AUTHOR]

The aim of the present study was to detect DACT1 expression levels in the lungs of children with asthma, and to investigate its role and molecular mechanisms in regulating the expression of inflammatory factors in RAW264.7 cells. DACT1, DACT2 and DACT3 expression was analyzed in biopsy specimens from 10 cases of newly diagnosed children with asthma and 10 healthy controls by reverse transcription‑quantitative polymerase chain reaction, and their expression was confirmed in RAW264.7 cells. DACT1 expression was silenced by small interfering RNA or enhanced by transfection of pcDNA‑3.1‑DACT1 in RAW264.7 cells, and expression of β‑catenin and inflammatory factors, interleukin (IL) 5, IL6 and IL13, was analyzed. Nuclear translocation of β‑catenin was detected by western blot analysis, and the effect of DACT1 on β‑catenin was investigated with rescue experiments. Regulation of the Wnt signaling pathway by DACT1 and β‑catenin was analyzed in RAW264.7 cells after recombinant Wnt5A stimulation. DACT1, DACT2 and DACT3 were significantly upregulated in specimens from children with asthma compared with controls (P<0.05) and the expression of DACT1 was significantly more increased compared with DACT2 and DACT3 (P<0.05). Inhibition of DACT1 expression significantly suppressed IL5, IL6 and IL13 mRNA expression levels compared with the control (P<0.05), while upregulated DACT1 expression significantly increased IL5, IL6 and IL13 mRNA expression (P<0.05). DACT1 inhibited the expression and nuclear translocation of β‑catenin, while overexpression of β‑catenin significantly inhibited the biological function of DACT1 (P<0.05). Overexpression of β‑catenin also significantly suppressed the upregulation of IL5, IL6 and IL13 mRNA induced by pcDNA3.1‑DACT1 transfection (P<0.05). Following the addition of Wnt5A, overexpression of DACT1 inhibited the expression and nuclear translocation of β‑catenin, and upregulated IL5, IL6 and IL13 mRNA expression. In conclusion, DACT1 was indicated to be upregulated in lung tissues from children with asthma, which could induce higher pro‑inflammatory factor expression. DACT1 may act via inhibiting the expression and nuclear translocation of β‑catenin, a factor in the Wnt signaling pathway. The present results suggested that DACT1 may be a potential target for the treatment of asthma. [ABSTRACT FROM AUTHOR]