Different phenotypes of non-classical monocytes associated with systemic inflammation, endothelial alteration and hepatic compromise in patients with dengue

Immunology. 2019 Feb;156(2):147-163. doi: 10.1111/imm.13011. Epub 2018 Nov 8.


Although dengue can progress to severe stages, the exact causes of this phenomenon are unknown; however, the possibility of monocyte participation is acknowledged. It has been suggested that monocyte subsets (classical, intermediate and non-classical) play differential roles in dengue immunopathology. Therefore, we determined the count of monocyte subsets and obtained the clinical information of patients with dengue. We noted a significant decrease in the count of non-classical monocytes in patients compared with controls. With this finding, we focused on studying the phenotype of non-classical monocytes in the present study. An increase in activation and differentiation markers, such as CD64, CD86, the percentage of tumor necrosis factor-α+ cells and exposure of phosphatidylserine, were recorded in the non-classical monocytes of patients compared with controls. Moreover, a significant decrease in the expression of CX3CR1 with a corresponding increase in the expressions of CCR2, CCR5, CD11b and CD54 was detected in the non-classical monocytes of patients in comparison with that of the controls. Significant increases in the frequency of microparticles from endothelium and in the concentrations of interleukin-6 (IL-6), IL-8 and IL-10 were noted in the plasma of patients. These findings demonstrate that in patients with dengue, non-classical monocytes are activated, exhibiting a phenotype associated with more differentiation, produces tumor necrosis factor-α and has a profile of less endothelial surveillance closer to the cellular migration. These changes were associated with hepatic compromise, endothelial alteration and high concentration of circulating cytokines. Hence, alterations of non-classical monocytes seem to be associated with the immunopathology of dengue infection.

Keywords: dengue; monocyte subsets; monocytes; non-classical monocytes; severe dengue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, CD / immunology
  • Cytokines / immunology
  • Dengue / immunology*
  • Dengue / pathology
  • Endothelium, Vascular / immunology*
  • Endothelium, Vascular / pathology
  • Female
  • Humans
  • Liver / immunology*
  • Liver / pathology
  • Male
  • Middle Aged
  • Monocytes / immunology*
  • Monocytes / pathology
  • Receptors, Chemokine / immunology
  • Systemic Inflammatory Response Syndrome / immunology*
  • Systemic Inflammatory Response Syndrome / pathology


  • Antigens, CD
  • Cytokines
  • Receptors, Chemokine