RESUMO
Dendritic cells (DCs) comprise two functionally distinct subsets: plasmacytoid DCs (pDCs) and myeloid DCs (mDCs). pDCs are specialized in rapid and massive secretion of type I interferon (IFN-I) in response to nucleic acids through Toll like receptor (TLR)-7 or TLR-9. In this report, we characterized a CD56(+) DC population that express typical pDC markers including CD123 and BDCA2 but produce much less IFN-I comparing with pDCs. In addition, CD56(+) DCs cluster together with mDCs but not pDCs by genome-wide transcriptional profiling. Accordingly, CD56(+) DCs functionally resemble mDCs by producing IL-12 upon TLR4 stimulation and priming naïve T cells without prior activation. These data suggest that the CD56(+) DCs represent a novel mDC subset mixed with some pDC features. A CD4(+)CD56(+) hematological malignancy was classified as blastic plasmacytoid dendritic cell neoplasm (BPDCN) due to its expression of characteristic molecules of pDCs. However, we demonstrated that BPDCN is closer to CD56(+) DCs than pDCs by global gene-expression profiling. Thus, we propose that the CD4(+)CD56(+) neoplasm may be a tumor counterpart of CD56(+) mDCs but not pDCs.
Assuntos
Humanos , Biomarcadores , Metabolismo , Antígeno CD56 , Genética , Alergia e Imunologia , Linhagem da Célula , Genética , Alergia e Imunologia , Células Dendríticas , Alergia e Imunologia , Metabolismo , Patologia , Expressão Gênica , Neoplasias Hematológicas , Genética , Alergia e Imunologia , Patologia , Imunofenotipagem , Interferon Tipo I , Metabolismo , Interleucina-12 , Metabolismo , Subunidade alfa de Receptor de Interleucina-3 , Genética , Alergia e Imunologia , Lectinas Tipo C , Genética , Alergia e Imunologia , Glicoproteínas de Membrana , Genética , Alergia e Imunologia , Células Mieloides , Alergia e Imunologia , Metabolismo , Patologia , Receptores Imunológicos , Genética , Alergia e Imunologia , Terminologia como Assunto , Receptor 4 Toll-Like , Genética , Alergia e Imunologia , Receptor 7 Toll-Like , Genética , Alergia e Imunologia , Receptor Toll-Like 9 , Genética , Alergia e ImunologiaRESUMO
The use of antiviral drugs such as influenza neuraminidase (NA) inhibitors is a critical strategy to prevent and control flu pandemic, but this strategy faces the challenge of emerging drug-resistant strains. For a highly pathogenic avian influenza (HPAI) H5N1 virus, biosafety restrictions have significantly limited the efforts to monitor its drug responses and mechanisms involved. In this study, a rapid and biosafe assay based on NA pseudovirus was developed to study the resistance of HPAI H5N1 virus to NA inhibitor drugs. The H5N1 NA pseudovirus was comprehensively tested using oseltamivir-sensitive strains and their resistant mutants. Results were consistent with those in previous studies, in which live H5N1 viruses were used. Several oseltamivir-resistant mutations reported in human H1N1 were also identified to cause decreased oseltamivir sensitivity in H5N1 NA by using the H5N1 NA pseudovirus. Thus, H5N1 NA pseudoviruses could be used to monitor HPAI H5N1 drug resistance rapidly and safely.
Assuntos
Animais , Humanos , Aves , Farmacorresistência Viral , Genética , Inibidores Enzimáticos , Usos Terapêuticos , Células HEK293 , Vírus da Influenza A Subtipo H1N1 , Genética , Virulência , Virus da Influenza A Subtipo H5N1 , Genética , Virulência , Influenza Aviária , Tratamento Farmacológico , Genética , Virologia , Influenza Humana , Tratamento Farmacológico , Genética , Virologia , Mutagênese Sítio-Dirigida , Neuraminidase , Genética , OseltamivirRESUMO
The aim of synthetic biology is to design artificial biological systems for novel applications. From an engineering perspective, construction of biological systems of defined functionality in a hierarchical way is fundamental to this emerging field. Here, we highlight some current advances on design of several basic building blocks in synthetic biology including the artificial gene control elements, synthetic circuits and their assemblies into devices and modules. Such engineered basic building blocks largely expand the synthetic toolbox and contribute to our understanding of the underlying design principles of living cells.