title: Decreased monocyte subsets and TLR4-mediated functions in patients with acute severe fever with thrombocytopenia syndrome (SFTS).
abstract: OBJECTIVE
  The role of a newly discovered bunyavirus, the severe fever with thrombocytopenia syndrome virus (SFTSV), in the pathogenesis of severe fever with thrombocytopenia syndrome (SFTS) is poorly understood. In this study, it was hypothesized that peripheral monocytes, which are constantly exposed to viral infection in the blood, are likely targeted by the causative virus in SFTS patients.
  
  
  METHODS
  Fifty-three patients and 25 healthy volunteers were enrolled in the study. Monocyte counts in the peripheral blood of all human subjects were monitored throughout the progress of the disease. SFTSV viral load and the expression of monocyte genes were investigated by real-time RT-PCR. Cytokine production of monocytes in SFTS patients upon lipopolysaccharide (LPS) stimulation was examined by ELISA.
  
  
  RESULTS
  In comparison to SFTS patients in the convalescent stage and healthy controls, monocyte cell counts and percentages in patients at the acute stage were significantly lower. Decreased monocyte cell counts and subsets were positively correlated with SFTSV viral loads in the serum samples from SFTS patients. Despite their higher basal toll-like receptor 4 (TLR4) expression, monocytes from patients in the acute phase were shown to be compromised regarding the production of tumor necrosis factor alpha, but not interleukin 10, upon LPS stimulation.
  
  
  CONCLUSIONS
  These data strongly suggest that monocytes could be a major target during SFTSV infection. The decreased population and dysfunction of monocytes in acute SFTS patients may contribute to the disease severity.
authors.affiliation: Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Liberation Avenue, Wuhan, 430027, PR China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Liberation Avenue, Wuhan, 430027, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Liberation Avenue, Wuhan, 430027, PR China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Liberation Avenue, Wuhan, 430027, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Liberation Avenue, Wuhan, 430027, PR China.
authors.forename: Qiaxia
authors.initials: Q
authors.lastname: Tong
authors.affiliation: Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Liberation Avenue, Wuhan, 430027, PR China.
authors.forename: Shenghua
authors.initials: S
authors.lastname: Jie
authors.affiliation: Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Liberation Avenue, Wuhan, 430027, PR China.
authors.forename: Dongliang
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Liberation Avenue, Wuhan, 430027, PR China. Electronic address: yingchunzhou@hust.edu.cn.
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000208:Acute Disease; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D002044:Bunyaviridae Infections / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D002681:China / Q000453:epidemiology; D005260:Female; D005334:Fever / Q000821:virology*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes; D016856:Phlebovirus / Q000235:genetics / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D013921:Thrombocytopenia / Q000276:immunology* / Q000821:virology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019562:Viral Load
chemical_list: D000914:Antibodies, Viral; C508609:IL10 protein, human; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
keywords: Monocytes; Thrombocytopenia syndrome; Toll-like receptor 4; Viral infection