Expression of CD206 and CD163 on intermediate CD14 ++ CD16 + monocytes are increased in hemorrhagic fever with renal syndrome and are correlated with disease severity

Virus Res. 2018 Jul 15;253:92-102. doi: 10.1016/j.virusres.2018.05.021. Epub 2018 May 29.


Background: Hantaan virus infection causes lethal hemorrhagic fever with renal syndrome (HFRS) in humans. Little is known about how monocytes contribute to HFRS pathogenesis. In this study, we aimed to investigate changes in various monocyte subsets in HFRS patients.

Methods: A total of 41 HFRS patients and 17 age-, sex-, and ethnicity-matched healthy control subjects were included in this study. Numbers/percentages of various monocyte subsets were quantitatively determined using flow cytometry. Serum levels of interleukin (IL)-10, IL-12, and tumor necrosis factor alpha (TNF-α) were detected using a cytometric bead array (CBA).

Results: CD14++CD16+ intermediate monocytes were significantly higher in HFRS patients compared to healthy controls (P < 0.01), especially during the acute phase. The expression of both CD163 and CD206 on CD14++CD16+ intermediate monocytes were increased during the acute phase of HFRS (P < 0.01 and P < 0.05, respectively) when comparing the convalescent phase and healthy controls. Furthermore, the numbers of CD14++CD16+ monocytes during the acute phase, and the percentages of CD14++CD16+CD163+ monocytes in patients with severe/critical HFRS were much higher compared to patients with mild/moderate HFRS. This also positively correlated with increased levels of white blood cells (WBC), blood urea nitrogen (BUN), and creatinine (Cr). However, the percentages of CD14++CD16+CD206+monocytes were higher in mild/moderate HFRS than in severe/critical HFRS, and they negatively correlated with platelets (PLT) and Cr.

Conclusions: Higher frequency of the CD14++CD16+ intermediate monocytes and increased expression of CD163+ and CD206+ markers on CD14++CD16+ monocytes were detected in patients with HFRS. The changes in the frequency of CD14++CD16+ monocytes and expression of CD163 and CD206 markers on CD14++CD16+ monocytes positively correlated with the severity of HFRS.

Keywords: Cytokine; Hemorrhagic fever with renal syndrome (HFRS); Monocyte.

MeSH terms

  • Adult
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Antigens, Differentiation, Myelomonocytic / genetics
  • Antigens, Differentiation, Myelomonocytic / metabolism*
  • Case-Control Studies
  • Female
  • Flow Cytometry
  • Hantaan virus / physiology
  • Hemorrhagic Fever with Renal Syndrome / genetics
  • Hemorrhagic Fever with Renal Syndrome / metabolism*
  • Hemorrhagic Fever with Renal Syndrome / pathology
  • Hemorrhagic Fever with Renal Syndrome / virology
  • Humans
  • Interleukin-10 / blood
  • Interleukin-12 / blood
  • Kidney Diseases / genetics
  • Kidney Diseases / metabolism*
  • Kidney Diseases / pathology
  • Kidney Diseases / virology
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism*
  • Lipopolysaccharide Receptors / genetics
  • Lipopolysaccharide Receptors / metabolism*
  • Male
  • Mannose Receptor
  • Mannose-Binding Lectins / genetics
  • Mannose-Binding Lectins / metabolism*
  • Middle Aged
  • Monocytes / metabolism*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Receptors, IgG / genetics
  • Receptors, IgG / metabolism*
  • Severity of Illness Index
  • Tumor Necrosis Factor-alpha / blood
  • Young Adult


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • IL10 protein, human
  • Lectins, C-Type
  • Lipopolysaccharide Receptors
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • Receptors, IgG
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12