Monocytes are effector immune cells but a precise anal-ysis of their role in immune response has been preclud-ed by their heterogeneity. Indeed, human monocytesare composed of at least three different subsets withdiff...Monocytes are effector immune cells but a precise anal-ysis of their role in immune response has been preclud-ed by their heterogeneity. Indeed, human monocytesare composed of at least three different subsets withdifferent phenotypic characteristics and functional prop-erties, the so-called classical, intermediate and non-classical monocytes. A review of the literature showsthat these monocyte subsets are differently affectedduring viral, bacterial, parasitic and fungal infections.The expansion of the CD16＋ compartment （intermedi-ate and non-classical monocytes） is typically observedin the majority of infectious diseases and the increasedproportion of CD16＋ monocytes is likely related totheir activation through their direct interaction with thepathogen or the infammatory context. In contrast, thenumber of non-classical and intermediate monocytesis decreased in Q fever endocarditis, suggesting thatcomplex mechanisms govern the equilibrium among monocyte subsets. The measurement of monocyte sub-sets would be useful in better understanding of the role of monocyte activation in the pathophysiology of infec-tious diseases.展开更多
Adenosine,a critical molecule regulating cellular function both inside and outside cells,is controlled by two human adenosine deaminases:ADA1 and ADA2.While ADA1 primarily resides in the cytoplasm,ADA2 can be transpor...Adenosine,a critical molecule regulating cellular function both inside and outside cells,is controlled by two human adenosine deaminases:ADA1 and ADA2.While ADA1 primarily resides in the cytoplasm,ADA2 can be transported to lysosomes within cells or secreted outside the cell.Patients with ADA2 deficiency(DADA2)often suffer from systemic vasculitis due to elevated levels of TNF-α in their blood.Monocytes from DADA2 patients exhibit excessive TNF-α secretion and differentiate into pro-inflammatory M1-type macrophages.Our findings demonstrate that ADA2 localizes to endolysosomes within macrophages,and its intracellular concentration decreases in cells secreting TNF-α.This suggests that ADA2 may function as a lysosomal adenosine deaminase,regulating TNF-α expression by the cells.Interestingly,pneumonia patients exhibit higher ADA2 concentrations in their bronchoalveolar lavage(BAL),correlating with elevated pro-inflammatory cytokine levels.Conversely,cord blood has low ADA2 levels,creating a more immunosuppressive environment.Additionally,secreted ADA2 can bind to apoptotic cells,activating immune cells by reducing extracellular adenosine levels.These findings imply that ADA2 release from monocytes during inflammation,triggered by growth factors,may be crucial for cell activation.Targeting intracellular and extracellular ADA2 activities could pave the way for novel therapies in inflammatory and autoimmune disorders.展开更多
文摘Monocytes are effector immune cells but a precise anal-ysis of their role in immune response has been preclud-ed by their heterogeneity. Indeed, human monocytesare composed of at least three different subsets withdifferent phenotypic characteristics and functional prop-erties, the so-called classical, intermediate and non-classical monocytes. A review of the literature showsthat these monocyte subsets are differently affectedduring viral, bacterial, parasitic and fungal infections.The expansion of the CD16＋ compartment （intermedi-ate and non-classical monocytes） is typically observedin the majority of infectious diseases and the increasedproportion of CD16＋ monocytes is likely related totheir activation through their direct interaction with thepathogen or the infammatory context. In contrast, thenumber of non-classical and intermediate monocytesis decreased in Q fever endocarditis, suggesting thatcomplex mechanisms govern the equilibrium among monocyte subsets. The measurement of monocyte sub-sets would be useful in better understanding of the role of monocyte activation in the pathophysiology of infec-tious diseases.
基金supported by Guangzhou Women and Children’s Hospital,Guangzhou Science and Technology Project(No.202201011494 to Liang Dong),and a grant(No.256053 to Andrey V.Zavialov)from the Finnish Academy.
文摘Adenosine,a critical molecule regulating cellular function both inside and outside cells,is controlled by two human adenosine deaminases:ADA1 and ADA2.While ADA1 primarily resides in the cytoplasm,ADA2 can be transported to lysosomes within cells or secreted outside the cell.Patients with ADA2 deficiency(DADA2)often suffer from systemic vasculitis due to elevated levels of TNF-α in their blood.Monocytes from DADA2 patients exhibit excessive TNF-α secretion and differentiate into pro-inflammatory M1-type macrophages.Our findings demonstrate that ADA2 localizes to endolysosomes within macrophages,and its intracellular concentration decreases in cells secreting TNF-α.This suggests that ADA2 may function as a lysosomal adenosine deaminase,regulating TNF-α expression by the cells.Interestingly,pneumonia patients exhibit higher ADA2 concentrations in their bronchoalveolar lavage(BAL),correlating with elevated pro-inflammatory cytokine levels.Conversely,cord blood has low ADA2 levels,creating a more immunosuppressive environment.Additionally,secreted ADA2 can bind to apoptotic cells,activating immune cells by reducing extracellular adenosine levels.These findings imply that ADA2 release from monocytes during inflammation,triggered by growth factors,may be crucial for cell activation.Targeting intracellular and extracellular ADA2 activities could pave the way for novel therapies in inflammatory and autoimmune disorders.
