Abstract
Aspergillosis is a common cause of morbidity and mortality in immunocompromised populations. CD23 is a novel C-type lectin receptors (CLR) recognizing α-mannan and β-glucan in the cell wall of Aspergillus fumigatus (AF) that exerts a host innate immune response. However, the molecular mechanism underlying CD23 mediating immunity against AF infection in human alveolar macrophages is still unclear. In this study, we detected the expression of CD23 and PU.1 and the inflammatory markers IL-1β, IL-6, TNF-α and IL-10 by qRT–PCR, Western blotting and enzyme linked immunosorbent assay (ELISA) analysis in human alveolar macrophages (AMs) with AF infection. Phagocytosis of macrophages with altered CD23 expression and histological changes in lung tissues transfected with CD23-expressing adenoviruses in AF infection were investigated. Dual luciferase, chromatin immunoprecipitation assay (ChIP) and electrophoretic mobility shift assay (EMSA) was performed to detect the interaction of PU.1 and CD23. The results showed that the expression of CD23, PU.1 and these inflammatory markers increased significantly with the time of AF infection. Increasing CD23 expression strengthened the phagocytosis of AMs, and exogenous CD23 attenuated pathological defects in immunodeficient mouse lung tissues with AF infection. Moreover, CD23 was directly activated by PU.1. PU.1 siRNA resulted in downregulation of inflammatory marker expression, but overexpression of CD23 significantly increased the expression of these markers. Our study concluded that CD23 mediates innate immunity against AF in human AMs through activation of PU.1. Therefore, PU.1/CD23 may be a new anti-aspergillosis therapeutic for the treatment of invasive aspergillosis with the deepening of gene therapy and its wide application in the clinic.
JNK1 negatively controls antifungal innate immunity by suppressing CD23 expression
