Immunomodulatory Effects of Newcastle Disease Virus AF2240 Strain on Human Peripheral Blood Mononuclear Cells

Abstract

Immunotherapy has raised the attention of many scientists because it hold promise to be an attractive therapeutic strategy to treat a number of disorders. In this study, the immunomodulatory effects of low titers of Newcastle disease virus (NDV) AF2240 on human peripheral blood mononuclear cells (PBMC) were analyzed. We evaluated cytokine secretion and PBMC activation by cell proliferation assay, immunophenotyping and enzyme linked immunosorbent assay. The proliferation of the human PBMC was measured to be 28.5% and 36.5% upon treatment with 8 hemaglutinin unit (HAU) and 2 HAU of NDV respectively. Interestingly, the percentage of cells with activating markers CD16 and CD56 were increased significantly. Furthermore, the intracellular perforin and granzyme levels were also increased upon virus infection. Human PBMC treated with NDV titer 8 HAU was found to stimulate the highest level of cytokine production including interferon-γ, interleukin-2 and interleukin-12. The release of these proteins contributes to the antitumor effect of PBMC against MCF-7 breast cancer cells. Based on the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay, activated human PBMC showed high cytolytic efficiency towards human breast tumor cells. In summary, NDV was able to stimulate PBMC proliferation, cytokine secretion and cytolytic activity.

Antitumor and immunostimulatory activities of a genotype V recombinant attenuated veterinary Newcastle disease virus vaccine

“…Only a recombinant version of the virus expressing interleukin (IL)-2 enhanced the concentration of IFN-γ in supernatant, when compared to control groups (21). Recently, employing a genotype VIII velogenic strain (AF2240) over human PBMC, it was demonstrated the capacity of this strain to stimulate IFN-γ production (17). Here, we found that PBMC (except from donor 4) respond to rNDV-P05 and LPS with an upregulation in IFN-γ secretion.…”

“…An increase at mRNA level was also observed. Our results highlight that although rNDV-P05 is recombinantly attenuated, it triggers a similar effect when compared with a velogenic strain (17), without needing the expression of foreign cytokines, such as IL-2 (21). The upregulation in IFN-γ induced by rNDV on human PBMC could be beneficial in vivo, due to IFN-γ is involved in activating anticancer immunity (T cells, NK cells and DCs), in inhibiting the activity of immune-suppressive cells (regulatory T cells and myeloid-derived suppressor cells), as well as in the conversion of tumor-associated macrophages (58,59).…”

“…Besides, NDV can also develop additional immune stimulatory mechanisms. It is known that it provokes the release of danger signals during virus replication into the tumor cell cytoplasm (14)(15)(16) and stimulates the immune system to produce cytokines such as interferons (IFNs) or TNF (17). In turn, these inflammatory cytokines lead to the activation of natural killer (NK) cells, monocytes, macrophages and sensitized T cells, stimulating both innate and adaptive immune response (17)(18)(19)(20)(21).…”

Bioactive Fraction from Datura stramonium Linn. Promotes Human immune Cells Mediated Cytotoxicity towards Lung and Breast Cancer Cells

“…Previously it has been reported that these cytokines play an important role in innate/acquired immune responses and tumor suppression 34 as IFN-γ and IL-2 have the ability to activate immune cells including macrophages, NK cells and CTLs which have well known cancer cell killing capabilities. 35,36 The increased level of IFN-γ and IL-2 indicates that D. stramonium fraction-10 might be stimulating anticancer immune responses mediated through human lymphocytes. Taken together, present research explored the in vitro immunostimulatory potential of bioactive fraction-10 from D. stramonium that boosts the immune cells and enhances their anticancer abilities against human lung and breast cancer cells.…”

DNA Replication: From Radioisotopes to Click Chemistry

“…The approaches based on the immuno-detection of halogen derivatives are very important procedures used for the detection of the replicational activity of cells, and serve as an important tool for the description of cellular proliferation and cell cycle by microscopy or flow cytometry as well, e.g., [ 57 , 58 , 59 , 60 , 61 , 62 , 63 ]. They also enabled researchers to collect a new data about the organization of replication.…”