Dengue-2 infection and the induction of apoptosis in human primary monocytes

Monocytes/macrophages are important targets for dengue virus (DENV) replication; they induce inflammatory mediators and are sources of viral dissemination in the initial phase of the disease. Apoptosis is an active process of cellular destruction genetically regulated, in which a complex enzymatic pathway is activated and may be trigged by many viral infections. Since the mechanisms of apoptotic induction in DENV-infected target cells are not yet defined, we investigated the virus-cell interaction using a model of primary human monocyte infection with DENV-2 with the aim of identifying apoptotic markers. Cultures analyzed by flow cytometry and confocal microscopy yielded DENV antigen positive cells with rates that peaked at the second day post infection (p.i.), decayed afterwards and produced the apoptosis-related cytokines TNF-á and IL-10. Phosphatidylserine, an early marker for apoptosis, was increased at the cell surface and the Fas death receptor was upregulated at the second day p.i. at significantly higher rates in DENV infected cell cultures than controls. However, no detectable changes were observed in the expression of the anti-apoptotic protein Bcl-2 in infected cultures. Our data support virus modulation of extrinsic apoptotic factors in the in vitro model of human monocyte DENV-2 infection. DENV may be interfering in activation and death mechanisms by inducing apoptosis in target cells.

Evaluation of anticardiolipin antibodies and antiphosphatidylserine antibodies in women with recurrent abortion.

BACKGROUND: Antiphospholipid syndrome (APS) is a major reproductive complication in women, which is characterized by recurrent fetal loss, thrombosis, and thrombocytopenia in association with anticardiolipin antibodies (aCL). AIMS: To analyze the prevalence of aCL and antiphosphatidylserine antibodies (aPS) in relation to pregnancy failures in women with the history of recurrent spontaneous abortion. SETTINGS AND DESIGN: A sequential study of 155 patients, who had three or more recurrent spontaneous abortions, was carried out. METHODS AND MATERIALS: Women with unexplained recurrent pregnancy loss in first trimester were selected for this study. Anticardiolipin antibodies IgG and aPS IgG were detected in the serum by the enzyme linked immunosorbent assay method. STATISTICAL ANALYSIS: Percentage calculation was carried out. Two-tailed t-test was performed to know the significance of aCL and aPS total population. RESULT: The levels of aCL IgG and aPS IgG were detected as 40% (62) and 19% (18), respectively in women with history of recurrent abortion. CONCLUSION: Anticardiolipin antibody is found to be the most important factor for recurrent abortion. In addition, women with negative aCL are having positive for another antiphospholipid antibodies like aPS, which may involve in recurrent abortion.

Apoptotic mimicry: an altruistic behavior in host/Leishmania interplay

Apoptosis is the most common phenotype observed when cells die through programmed cell death. The morphologic and biochemical changes that characterize apoptotic cells depend on the activation of a diverse set of genes. Apoptosis is essential for multicellular organisms since their development and homeostasis are dependent on extensive cell renewal. In fact, there is strong evidence for the correlation between the emergence of multicellular organisms and apoptosis during evolution. On the other hand, no obvious advantages can be envisaged for unicellular organisms to carry the complex machinery required for programmed cell death. However, accumulating evidence shows that free-living and parasitic protozoa as well as yeasts display apoptotic markers. This phenomenon has been related to altruistic behavior, when a subpopulation of protozoa or yeasts dies by apoptosis, with clear benefits for the entire population. Recently, phosphatidylserine (PS) exposure and its recognition by a specific receptor (PSR) were implicated in the infectivity of amastigote forms of Leishmania, an obligatory vertebrate intramacrophagic parasite, showing for the first time that unicellular organisms use apoptotic features for the establishment and/or maintenance of infection. Here we focus on PS exposure in the outer leaflet of the plasma membrane - an early hallmark of apoptosis - and how it modulates the inflammatory activity of phagocytic cells. We also discuss the possible mechanisms by which PS exposure can define Leishmania survival inside host cells and the evolutionary implications of apoptosis at the unicellular level.