Kinetic Changes of Peripheral Blood Monocyte Subsets and Expression of Co-Stimulatory Molecules during Acute Dengue Virus Infection.

Sakaorat Lertjuthaporn,Korakot Polsrila,Ladawan Khowawisetsut,Aftab A Ansari,Kulkanya Chokephaibulkit,Kasama Sukapirom,Ampaiwan Chuansumrit,Rassamon Keawvichit,Kovit Pattanapanyasat

doi:10.3390/pathogens10111458

Abstract

Monocytes, one of the main target cells for dengue virus (DENV) infection, contribute to the resolution of viremia and to pathogenesis. We performed a longitudinal study by a detailed phenotypic comparison of classical (CD14++CD16−, non-classical (CD14+CD16++) and intermediate (CD14++CD16+) monocyte subsets in blood samples from dengue fever (DF) to the severe dengue hemorrhagic fever (DHF) and healthy individuals. Various costimulatory molecules of CD40, CD80, CD86 and inducible costimulatory ligand (ICOSL) expressed on these three monocyte subsets were also analyzed. DENV-infected patients showed an increase in the frequency of intermediate monocytes and a decrease in the classical monocytes when compared to healthy individuals. Although these differences did not correlate with disease severity, changes during the early phase of infection gradually returned to normal in the defervescence phase. Moreover, decreased frequency of classical monocytes was associated with a significant up-regulation of co-stimulatory molecules CD40, CD86 and ICOSL. Kinetics of these co-stimulatory molecule-expressing classical monocytes showed different patterns throughout the sampling times of acute DENV infection. Different distribution of monocyte subsets and their co-stimulatory molecules in the peripheral blood during acute infection might exacerbate immune responses like cytokine storms and ADE, and future studies on intracellular molecular pathways utilized by these monocyte linages are warranted.

Highlights

Dengue virus (DENV) infection is one of the most significant emerging diseases that affects nearly 100 million people annually in over 100 countries, occurring predominantly in countries within the tropical and sub-tropical regions [1]
The kinetics of the frequencies of classical monocytes from DENV-infected patients were significantly decreased at day −2 (D −2) (p = 0.003), D −1 (p < 0.0001) and Day 0 (D0) (p = 0.01) when compared with the mean values obtained from healthy individuals (Figure 1E)
While there was no significant difference in the frequencies of non-classical monocytes between healthy individuals and DENV-infected patients (Figure 1D and Table 1), in the kinetic studies the frequency of non-classical monocytes showed a small increase that returned to normal levels during the afebrile phase (Figure 1G)

Summary

Introduction

Dengue virus (DENV) infection is one of the most significant emerging diseases that affects nearly 100 million people annually in over 100 countries, occurring predominantly in countries within the tropical and sub-tropical regions [1]. There have been several proposed hypotheses forwarded that attempt to describe the basis for such diverse outcomes of DENV infections These include exacerbated immune response with varying degrees of elevated levels of cytokines or cytokine storms, as well as antibody-dependent enhancement (ADE) [5,6]. The latter occurs predominantly either in patients with secondary heterologous DENV infections or in infants with primary infections born to mothers with established immunity [7,8,9]. These antibodies upon secondary heterotypic infection potentially lead to viral internalization via Fc receptors and enhanced replication within phagocytic cells followed by massive release of soluble factors capable of affecting endothelial cell damage and loss of platelet integrity that lead to DHF/DSS

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