Sporothrix schenckii regulates macrophage inflammatory responses via the c‐JUN‐induced Dab2 transcription

Abstract

Macrophages, which serve as a bridge between innate and adaptive immunity, play an important role in sporotrichosis. Sporothrix schenckii infections can produce immune responses such as macrophage polarization and inflammatory factor secretion. In the early stages of inflammation, the expression of DAB2 in macrophages is increased, which controls the secretion of inflammatory factors and affects the polarization of macrophages. However, the expressions and mechanisms of DAB2 in sporotrichosis are not clear. In this study, we examined the expression of DAB2 and its regulation of inflammatory factors under conditions of Sporothrix schenckii infection. Our results indicated that the Sporothrix schenckii infection increased the expression of DAB2 and revealed a mixed M1/M2‐like type of gene expression in BMDMs with the inhibited Il‐6, Il1‐β and Arg‐1 and induced Tnf‐α, Il‐10 and Mgl‐1. The deficiency of Dab2 gene suspended the changes of cytokines. In addition, JNK activity in BMDMs was inhibited by Sporothrix schenckii infection, leading to an increase in c‐JUN. We also identified c‐JUN as a transcription factor for Dab2 through chromatin immunoprecipitation and luciferase reporter assays. In an in vivo mouse model, sporotrichosis‐induced skin lesions were accompanied with an upregulation of c‐JUN and inhibition of JNK activity, which were in accord with findings from in vitro experiments. Taken together, these findings indicate that in the early stages of Sporothrix schenckii infection there is a promotion of DAB2 expression through the JNK/c‐JUN pathway, effects that can then control the expression of inflammatory factors.

Icariin attenuates asthmatic airway inflammation via modulating alveolar macrophage activation based on network pharmacology and in vivo experiments

“…The transcriptional activity of AP1 can be inhibited by DEX 93 . Notably, a recent study noted that, with the increased activity of Jun , the levels of M1 and M2 biomarkers are elevated and decreased respectively 94 . The inhibition of Jun significantly diminishes inflammatory cells encroaching on the airway lumen 95 .…”

“…93 Notably, a recent study noted that, with the increased activity of Jun, the levels of M1 and M2 biomarkers are elevated and decreased respectively. 94 The inhibition of Jun significantly diminishes inflammatory cells encroaching on the airway lumen. 95 TNF, a pro-inflammatory mediator, contributes to airway inflammation and AHR in asthma through immunoregulation.…”

Skin innate immune response against fungal infections and the potential role of trained immunity

“…and Scedosporium spp., respectively, can be recognized by TLR4 leading to the induction of TNF‐α and IL‐6 40 . Meanwhile, TLR2, TLR4/CR3 was described as important for phagocytosis of the yeast form of S. schenckii and S. brasiliensis by macrophages through interaction with peptidorhamnomannans 41,42 …”

“…40 Meanwhile, TLR2, TLR4/CR3 was described as important for phagocytosis of the yeast form of S. schenckii and S. brasiliensis by macrophages through interaction with peptidorhamnomannans. 41,42 Macrophages along with other innate and adaptive cells play a crucial role in the formation of granuloma. The granuloma is formed when these cells accumulate at the site of infection to prevent the spread of the pathogen.…”