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      In vitro study of the effect of a probiotic bacterium Lactobacillus rhamnosus against herpes simplex virus type 1

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          Abstract

          BACKGROUND: Due to the emergence of drug resistance in herpes simplex virus type 1 (HSV-1), researchers are trying to find other methods for treating herpes simplex virus type 1 infections. Probiotic bacteria are effective in macrophage activation and may have antiviral activities. OBJECTIVE: This study aimed at verifying the direct effect of Lactobacillus rhamnosus, a probiotic bacterium, in comparison with Escherichia coli, a non-probiotic one, on HSV-1 infection, and determining its effect on macrophage activation for in vitro elimination of HSV-1 infection. METHODS: The above bacteria were introduced into HSV-1 infected Vero cells, and their effects were examined using both MTT and plaque assay. To determine macrophage activation against in vitro HSV-1 infection, J774 cells were exposed to these bacteria; then, macrophage viability was examined with the MTT method, and tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), and nitric oxide (NO) assessments were performed using the ELISA method. RESULTS: A significant increased viability of macrophages was observed (p < 0.05) in the presence of Lactobacillus rhamnosus before and after HSV-1 infection when compared with Escherichia coli as a non-probiotic bacterium. However, tumor necrosis factor α concentration produced by Escherichia coli-treated J774 cells was significantly higher than Lactobacillus rhamnosus-treated J774 cells (p < 0.05). interferon-gamma and NO production were not different in the groups treated with Escherichia coli or with Lactobacillus rhamnosus. CONCLUSION: The results of this study indicate that Lactobacillus rhamnosus enhances macrophage viability for HSV-1 elimination and activation against HSV-1 more effectively, when compared with non-probiotic Escherichia coli. it also seems that receptor occupation of macrophage sites decreases HSV-1 infectivity by both of the studied bacteria.

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          Interleukin-12 is involved in the enhancement of human natural killer cell activity by Lactobacillus casei Shirota.

          We conducted a placebo-controlled, cross-over trial to examine the effect of Lactobacillus casei Shirota (LcS) on natural killer (NK) cell activity in humans. NK cell activity exhibited a declining trend during the period of placebo ingestion, but NK cell activity increased after intake for 3 weeks of fermented milk containing 4 x 10(10) live LcS. When human peripheral blood mononuclear cells were cultured in the presence of heat-killed LcS, NK cell activity was enhanced. The ability of LcS to enhance NK cell activity and induce interleukin (IL)-12 production was correlated, and the addition of anti-IL-12 monoclonal antibody reduced the enhancement of NK cell activity triggered by LcS. In addition, separation of NK cells from LcS-stimulated monocytes with membrane filter reduced NK cell activity to the intermediate level and almost deprived monocytes of the ability to produce IL-12. These results demonstrate that LcS can enhance NK cell activity in vivo and in vitro in humans, and IL-12 may be responsible for enhancement of NK cell activity triggered by LcS.
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            Macrophages and cytokines in the early defence against herpes simplex virus

            Herpes simplex virus (HSV) type 1 and 2 are old viruses, with a history of evolution shared with humans. Thus, it is generally well-adapted viruses, infecting many of us without doing much harm, and with the capacity to hide in our neurons for life. In rare situations, however, the primary infection becomes generalized or involves the brain. Normally, the primary HSV infection is asymptomatic, and a crucial element in the early restriction of virus replication and thus avoidance of symptoms from the infection is the concerted action of different arms of the innate immune response. An early and light struggle inhibiting some HSV replication will spare the host from the real war against huge amounts of virus later in infection. As far as such a war will jeopardize the life of the host, it will be in both interests, including the virus, to settle the conflict amicably. Some important weapons of the unspecific defence and the early strikes and beginning battle during the first days of a HSV infection are discussed in this review. Generally, macrophages are orchestrating a multitude of anti-herpetic actions during the first hours of the attack. In a first wave of responses, cytokines, primarily type I interferons (IFN) and tumour necrosis factor are produced and exert a direct antiviral effect and activate the macrophages themselves. In the next wave, interleukin (IL)-12 together with the above and other cytokines induce production of IFN-γ in mainly NK cells. Many positive feed-back mechanisms and synergistic interactions intensify these systems and give rise to heavy antiviral weapons such as reactive oxygen species and nitric oxide. This results in the generation of an alliance against the viral enemy. However, these heavy weapons have to be controlled to avoid too much harm to the host. By IL-4 and others, these reactions are hampered, but they are still allowed in foci of HSV replication, thus focusing the activity to only relevant sites. So, no hero does it alone. Rather, an alliance of cytokines, macrophages and other cells seems to play a central role. Implications of this for future treatment modalities are shortly considered.
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              Human monocytes/macrophages: NO or no NO?

              The production of nitric oxide (NO) and other reactive nitrogen intermediates by cytokine-activated rodent cells is an important component of antimicrobial and/or antineoplastic activity of these cells. This pathway involves the oxidation of arginine to citrulline, with the concomitant release of NO by an inducible form of NO synthase (iNOS). Numerous cell types express iNOS after stimulation with bacterial products and/or cytokines. The role of NO and its derivatives in host resistance is a subject of intense investigation in mouse models of infections or neoplasia. Although human cells such as hepatocytes and endothelial cells have been shown to express an inducible NO synthase, the presence of such a pathway in human monocytes/macrophages has been questioned by many investigators and is a subject of great controversy. In this short review, we discuss some salient points of this debate.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                bjid
                Brazilian Journal of Infectious Diseases
                Braz J Infect Dis
                Brazilian Society of Infectious Diseases (Salvador )
                1678-4391
                April 2012
                : 16
                : 2
                : 129-135
                Affiliations
                [1 ] Shiraz University of Medical Sciences Iran
                [2 ] Shiraz University of Medical Sciences Iran
                [3 ] Tabriz University of Medical Sciences Iran
                Article
                S1413-86702012000200004
                10.1590/S1413-86702012000200004
                1a5950e9-dd16-4880-addf-a29704fc1907

                http://creativecommons.org/licenses/by/4.0/

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                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=1413-8670&lng=en
                Categories
                INFECTIOUS DISEASES

                Infectious disease & Microbiology
                Probiotic,Lactobacillus rhamnosus,Herpes simplex virus type 1

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