PU.1 serves a critical role in the innate defense against Aspergillus fumigatus via dendritic cell-associated C-type lectin receptor-1 and toll-like receptors-2 and 4 in THP-1-derived macrophages
نویسندگان
چکیده
Aspergillus fumigatus (A. fumigatus) is one of the most common fungal pathogens of invasive pulmonary aspergillosis (IPA), which may be life threatening in immunocompromised individuals. The dendritic cell-associated C-type lectin receptor (Dectin-1), toll‑like receptor (TLR)-2 and TLR-4 are major pattern recognition receptors in alveolar macrophages that recognize A. fumigatus components. The PU.1 transcription factor is known to be important for the transcriptional control of these three receptors in mature macrophages. The present study investigated whether alterations of PU.1 expression may affect the innate defense against A. fumigatus in the human monocyte THP‑1 cell line. THP-1-derived macrophages were transduced with PU.1 adenoviral vectors and transfected with PU.1 small interfering RNA, and the mRNA and protein expression levels of Dectin‑1, TLR‑2 and TLR‑4 were measured. In addition, the levels of tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β were ascertained, and fungal phagocytosis and killing were assessed. The results demonstrated that overexpression of PU.1 by recombinant adenoviral vectors resulted in a significant upregulation of Dectin‑1, TLR‑2 and TLR‑4 at the transcriptional and translational levels. In response to A. fumigatus stimulation, PU.1 overexpression increased TNF‑α and IL‑1β production. In addition, Dectin‑1, TLR‑2 and TLR‑4 upregulation may have enhanced the phagocytosis and killing ability of THP‑1‑derived macrophages. As expected, silencing of PU.1 led to downregulation of Dectin‑1, TLR‑2, TLR‑4 and the expression of pro‑inflammatory cytokines, as well as decreased phagocytosis and the killing ability of THP1‑derived macrophages. In conclusion, the results indicate that PU.1 may be a critical factor for the innate defense against A. fumigatus, and may therefore be a potential target for the prophylaxis and treatment of IPA.
منابع مشابه
Evaluating the Effects of Cytomegalovirus Glycoprotein B on the Maturation and Function of Monocyte-derived dendritic cells
Background & Objectives: Interaction of cytomegalovirus glycoprotein B with toll-like receptors of dendritic cells leads to early signaling and innate immune responses. The aim of this study is to evaluate the effects of cytomegalovirus glycoprotein B on the maturation and function of monocyte-derived dendritic cells in treated groups in comparison with control groups. Materials & Methods: Bloo...
متن کاملToll like receptor 5 (TLR5) may be involved in the immunological response to Aspergillus fumigatus in vitro.
Toll-like receptors (TLRs) are involved in the host defense against Aspergillus fumigatus infections, and some TLRs may even be exploited by the mould to escape immune mechanisms. We have previously shown that conidia from A. fumigatus increase expression of TLR5 in human monocytes. When further investigating a possible role of TLR5 in A. fumigatus infections, we observed a decrease in conidial...
متن کاملIn silico Study of Toll-Like Receptor 4 Binding Site of FimH from Uropathogenic Escherichia coli
Introduction : The innate immune system as the first line of defense against the pathogens recognizes pathogen-associated molecular patterns (PAMPs) by Toll-Like Receptors (TLRs). Interaction of bacterial PAMPs by TLRs results in activation of innate and acquired immunity. FimH adhesin, a minor component of type 1 fimbriae encoded by Uropathogenic Escherichia coli (UPEC) is a PAMP of TLR4 tha...
متن کاملP-33: Expression of Toll-Like Receptor 2-3 Genes in Human Sertoli Cells
Background: Toll-like receptors (TLRs) constitute a major part of innate immunity, which can distinguish pathogen associate molecular pattern. Sertoli cells create a special immunological niche that protects somniferous tubules from auto antigens and pathogens. These cells are the only somatic cells in somniferous that protect testis cells against pathogens. The purpose of this study was to eva...
متن کاملThe Efficacy of Toll-Like Receptors in Awakening Dendritic Cell/Natural Killer Cell System for Eradication of Tumors
Natural killer (NK) cells are effector cells of the innate immune system that exert direct cytotoxic functions. Ubiquitously-expressed toll-like receptors (TLRs) have been recognized as one of the major components promoting dendritic cell (DC) maturation, which may induce polarized immune responses beneficial to cancer immunotherapy. TLR-activated NK cells and DCs are prerequisite for robust ac...
متن کامل