Role of Monocytes in the Pathogenesis of Dengue

Abstract

Diseases caused by dengue virus (DENV) are a major public health problem worldwide, considered one of the infections with more prevalence in tropical and subtropical zones of the world. Despite the intense research in the pathogenesis of DENV, this feature is not well understood. One of the main target cells for DENV infection is monocytes; these phagocytes can play a dual role, since they are essential to control viremia, but they also participate in the induction of tissue damage during DENV infection. Monocytes produce different pro-inflammatory cytokines and chemokines in response to infection, and also mediate endothelial damage. In peripheral blood, monocytes can be divided into three different subpopulations, namely classical, intermediate and non-classical, which differ in frequency, cytokine production, among others. Studies in the last years suggest that non-classical monocytes have higher affinity for microvasculature endothelium compared to other type of monocytes, which implies that they could be more involved in the increase of endothelial permeability observed during DENV infection. This review provides a general view of the role of monocytes and their subpopulations in DENV pathogenesis and its effect in viral replication. Finally, the potential contribution of these phagocytes in the alterations of endothelial permeability is discussed.

Possible roles of monocytes/macrophages in response to elephant endotheliotropic herpesvirus (EEHV) infections in Asian elephants (Elephas maximus)

“…In contrast to the present study, apoptosis of the peripheral blood mononuclear cells was predominantly observed in the fatal cases of EEHV1A-HD and EEHV4-HD infections and in a lower extent of persistent EEHV4-infection. Despite these findings may support the hypothesis indicating the functional role of monocytes in inhibiting the viral replication, as seen in the infection of dengue virus, PRRSV and FIPV [10,11,33,34], it remains unknown whether infection of EEHV in monocytes causes delay apoptosis. Moreover, since positive signals of TUNEL assay were also observed in the cytoplasm of peripheral blood monocytes, it is possible that in addition to the apoptotic bodies that seen in EEHV-infected monocytes, apoptotic bodies derived from the EEHV-infected cells may also had phagocytosed by the phagocytic cells, such as monocytes.…”

“…Monocytes/macrophages play a crucial role in the host defense mechanism against pathogen infections and dissemination [10][11][12][13][14]. During innate immune responses, monocytes/macrophages sense and promote inflammation by producing type 1 interferon and secreting proinflammatory cytokines, in order to recruit effecter cells to clear pathogens [15][16][17]; while in adaptive immune response, they serve as antigen-presenting cells prime to T lymphocytes [18].…”

“…During innate immune responses, monocytes/macrophages sense and promote inflammation by producing type 1 interferon and secreting proinflammatory cytokines, in order to recruit effecter cells to clear pathogens [15][16][17]; while in adaptive immune response, they serve as antigen-presenting cells prime to T lymphocytes [18]. Experimental inoculation of monocytes with dengue virus in vitro increased apoptosis of virus-infected cells and induced production of several inflammatory cytokines, including tumor necrosis factor-α (TNF-α) [10,11]. Apoptosis of monocytes/macrophages in dengue virus infection is believed to be an immunological process that inhibits virus replication in infected patients [10,11].…”

“…Experimental inoculation of monocytes with dengue virus in vitro increased apoptosis of virus-infected cells and induced production of several inflammatory cytokines, including tumor necrosis factor-α (TNF-α) [10,11]. Apoptosis of monocytes/macrophages in dengue virus infection is believed to be an immunological process that inhibits virus replication in infected patients [10,11]. However, to the best of our knowledge, no studies have investigated apoptosis of monocytes/macrophages in cases of EEHV infection.…”

Apoptosis characterization in mononuclear blood leukocytes of HIV patients during dengue acute disease

“…CD14 ++ CD16 − classical monocytes presented high phagocytic activity and they are critical for initial inflammatory responses while CD14 ++ CD16 + intermediate monocytes are associated with inflammatory response, and CD14 + CD16 ++ non-classical are considered as patrolling monocytes 21 . Monocyte activation has been reported during DENV and HIV infections and they are associated with disease pathogenesis 22,40 . Our results demonstrated significant changes of monocyte subsets during DENV and DENV/HIV coinfection.…”