Sortase A (SrtA), a type of transpeptidase responsible for anchoring surface proteins to the peptidoglycan cell wall, is important in the virulence of gram-positive bacteria. Three compounds were isolated from marine-derived Streptomyces sp. MBTH32 using various chromatography techniques. The structures of these compounds were determined based on spectroscopic data and comparisons with previously reported data. Among the metabolites tested, lumichrome showed strong inhibitory activity against Staphylococcus aureus SrtA without affecting cell viability. The results of cell clumping activity assessment suggest the potential for using this compound to treat S. aureus infection by inhibiting SrtA activity.
T cell exhaustion develops under conditions of antigen-persistence caused by infection with various chronic pathogens, such as human immunodeficiency virus (HIV) and myco-bacterium tuberculosis (TB), or by the development of cancer. T cell exhaustion is characterized by stepwise and progressive loss of T cell function, which is probably the main reason for the failed immunological control of chronic pathogens and cancers. Recent observations have detailed some of the intrinsic and extrinsic factors that influence the severity of T cell exhaustion. Duration and magnitude of antigenic activation of T cells might be associated with up-regulation of inhibitory receptors, which is a major intrinsic factor of T cell exhaustion. Extrinsic factors might include the production of suppressive cytokines, T cell priming by either non-professional antigenpresenting cells (APCs) or tolerogenic dendritic cells (DCs), and alteration of regulatory T (Treg) cells. Further investigation of the cellular and molecular processes behind the development of T cell exhaustion can reveal therapeutic targets and strategies for the treatment of chronic infections and cancers. Here, we report the properties and the mechanisms of T cell exhaustion in a chronic environment.
Observations were made on the differences in cell-mediated immune responses in the mice infected with strongly pathogenic Naegleria fewleyi ITMAP 359, weakly pathogenic Naegzeria jadini 0400, or non.pathogenic Naegleria gruberi EGB, respectively. Variations in cell-mediated responses and changes in antibody titers according to the duration after infection wore noted. Infections were done by dropping $5{\;}{\mu}l$ saline suspension containing $10{\times}10^4$ trophozoites cultured Bxenically in the CGVS medium into the right nasal cavity of ICR mice aging about 6~7 weeks, under the anesthesia by intraperitoneal injection of'secobarbital. Following infection, delayed type hypersensitivity(DTH) iesponses in the footpad and blastogenic responses of the mouse spleen cells using [$^3H$]-thymidine were observed on the day 1, 4, 7, 10 and 14 after infection. For the preparation of amoeba Iysates, each of cultured trophosoites were homogenized with an ultrasonicator, and centrifugated at 20,000 g. The supernatants of amoeba Iysates were used as the mitogen'and antigen for ELISA. Confanavalin A(Con. A) and lipopolysaccharide(LPS) were also used as mitogens in the blastogenic response. 1. The mice infected with N, fowleri showed the mortality rate of 75.7%. The rate was 6.2% for the N. jadini infected group, while no dead mouse was observed for N. gruberi infections. 2. In regard to DTH responses in the H. fewleri infected mice, the level increased in com- parison to the control group but declined after 7 days. An increase was also noted for the JV. jadini group after 1 day, but gradual decreases were observed through the infection period. In addition, no difference was noted between the N. gruberi infected and control groups. 3. Concerning the blastogenic response of the splenocytes, it increased after 10 days in the experimental group of N, fcwleri infection, but the differences ware not statistically significant compared with control group. It was evident that N. jadini group was not different from control group either, while there was a tendency of decrease in SV. gruberi infected group. In regard to the blastogenic response of the splenocytes by LPS, it was found that the N. fowlgri, N. jadini and N. gruberi infected groups had no differences from the control group. 4. The serum antibody titer of N. fcwleri and N. jadini infected mice increased from the day 7 and 14 after infection respectively, while the N. gruberi infected mice showed no increase. In summary of the results, it was observed that there were differences in the cell-mediated immune responses and serum antibody titers in the mice infected with strongly pathogenic JV. fowleri, weakly pathogenic N. jadini, or non.pathogenic N. gruberi, respectively.
Mohamed, Shereen H;Mahmoud, Nora F;Mohamed, Aly F;Kotb, Nahla S
Asian Pacific Journal of Cancer Prevention
/
v.16
no.14
/
pp.5635-5641
/
2015
Background: Cirrhosis is regarded as a possible end stage of many liver diseases, including viral infection. It occurs when healthy liver tissue becomes damaged and is replaced by scar tissue and finally may lead to hepatocellular carcinoma. Interferons (IFNs)are two general categories, type I and II. Type I includes one beta interferon and over 20 different alpha interferons. Alpha interferons are very similar in how they work, interacting with other proteins on cells like receptors. The main objective of this study was to compare Mx gene productivity post different cell line treatment with imported and Egyptian biosimilar locally produced IFNs, as well as the efficacy of those tested IFNs. Also, an assessment was made of sensitivity of different cell lines as alternatives to that recommended for evaluation of antiviral activity. Materials and Methods: Different cell lines (Vero, MDBK and Wish) were employed to evaluate cytotoxicity using the MTT assay. Antiviral activity was evaluated compared with standard IFN against VSV, Indiana strain -156, on tested rh-IFNs (imported; innovated and Egyptian biosimilar locally produced IFNs) in the pre-treated cell lines previously mentioned. The virus was propagated in the Wish cell line as recommended. Finally we estimated up-regulation of the Mx gene as a biomarker. Results: Data recorded revealed that test IFNs were safe in test cell lines. Viability was around 100%. Locally tested interferon did not realize the international potency limits, while the imported one was accepted compared with the standard IFN. These results were the same either using infectivity titer reduction assay or crystal violet staining of residual non- infected cells. Mx protein production was cell type related and confirmed by the detected Mx gene expressed in imported and locally produced IFN pre-treated cell lines. The expression of the gene was arranged in the order of Vero> wish > MDBK for the imported IFN, while for the Egyptian biosimillar locally produced one it was MDBK> Vero> wish. With regard to the antiviral activity there was a significant difference of imported IFN potency compared with the locally produced IFN (P<0.05), the IFN potential (antiviral activity) was not cell line related and showed non-significant difference for each separate product. Conclusions: Vero cells can be used as an alternative cell line for evaluation of IFN potency in case of unavailable USP recommended cell lines. Alternative potency evaluation assay could be used and proved significant difference in IFN potency in case of local and imported agents. Evaluation of antiviral activity could be used in parallel to viral infectivity reduction assay for better accuracy. Mx gene can be used as a marker for IFN potential.
Kim, Ok Kyung;Yoo, Seon A;Nam, Da-Eun;Kim, Yongjae;Kim, Eun;Jun, Woojin;Hwan, Kwontack;Lee, Jeongmin
Journal of the Korean Society of Food Science and Nutrition
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v.43
no.9
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pp.1317-1324
/
2014
The immune system protects the body against harmful substances and infectious agents. Normally, the body can maintain a state of immune homeostasis. However, failure of immune homeostasis results in severe diseases when the immune system is defective. We investigated the immunomodulatory effect of Curcuma longa L. extract in LP-BM5 MuLV (murine leukemia viruses)-induced murine AIDS (acquired immune deficiency syndrome). Mice were divided into six groups: normal control, infected control (LP-BM5 MuLV infection), positive control (LP-BM5 MuLV infection+dietary supplement of red ginseng 200 mg/kg), CL50 (LP-BM5 MuLV infection+dietary supplement of Curcuma longa L. 20% alcohol extract 50 mg/kg), CL200 (LP-BM5 MuLV infection+dietary supplement of Curcuma longa L. 20% alcohol extract 200 mg/kg), and CL500 (LP-BM5 MuLV infection+dietary supplement of Curcuma longa L. 20% alcohol extract 500 mg/kg). We found that dietary supplementation with Curcuma longa L. 20% alcohol extract inhibited elevation of spleen, lymph node, and liver weights as well as reduction of T- and B-cell proliferation and natural killer cell activity induced by LP-BM5 MuLV infection. Moreover, Curcuma longa L. 20% alcohol extract inhibited Th1 (IL-2, IFN-${\gamma}$)/Th2 (IL-4, IL-10) cytokine imbalance and pro-inflammatory cytokine production. In conclusion, these data suggest that Curcuma longa L. has immunomodulatory effects in LP-BM5 MuLV-induced murine AIDS.
Park, Jong-Chul;Lee, Jae-Dong;Seo, Jae-Hwan;Kim, Yang-Kil;Jeong, Seon-Gi;Kim, Hyung-Moo
Research in Plant Disease
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v.10
no.1
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pp.34-38
/
2004
The damage of plant growth and alteration of cellular tissues of barley infected by Barley yellow mosaic virus (BaYMV) was explored. The infected plots significantly damaged in all of measured factors by the disease. In severely diseased plant, the viral infection affected on plant growth like as shorten culm length about 25cm, 36% constrained ratio, comparing to healthy. The yield decreased over 70% in diseased plots by fewer numbers of spike and kernel per square meter and spike, respectively. BaYMV constructed typical inclusion body like a pinwheel type inside barley leaves, and the infection affected on cellular elongation or growth not cell division in examined three parts as stem, neck of panicle and node, related to dwarfness of infected barley. The stem tissues were most severely affected on cell growth as restrained epidermis cell length in diameter and vascular bundle size. In neck of panicle tissues, distribution and size of tissues of fiber and cortex parts, respectively, showed differences between healthy and infected plants. In node part, healthy plant showed bigger tissue size as 1.5 times than infected plant. Theses results suggest that BaYMV infection could affect on the cell growth not cell division, and which resulted shorten culm length in plant growth and decreased yield, finally.
Histopathological vascular changes in hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus include increased vascular permeability, disseminated intravascular coagulation, thrombocytopenia and changes in coagulation activity. Although vascular endothelial cells of main target organs such as kidney infected with Hantaan virus are not damaged but swelling of endothelial cells, perivascular exudates and infiltration of mononuclear cells and fresh interstitial hemorrhages are common. However, the pathogenesis of cell infiltration and hemorrhages around vascular endothelial cells are not well understood. Some endothelial cell molecules or vascular adhesins that acts as adhesion moleulces for leukocyte are expressed on endothelial cells close to site of inflammation. However, whether the expression of endothelial adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule (ICAM-1) and endothelial leukocyte adhesion molecule (ELAM) on vascular endothelial cells are increased by infection with Hantaan virus has not been studied. In this study, the relationship between the expression of VCAM-1, ICAM-1 and ELAM and adhesion of mononuclear cells on endothelial cells of human blood vessels infected with Hantaan virus was investigated. The endothelial cells of umbilical vein was passaged three times in culture medium and the monolayered cells were infected with $10^5\;pfu/ml$ of Hantaan virus grown in Vera E6 cell cultures. The multiplication of virus in cultured endothelial cells was monitored by immunohistochemistry and the expression of adhesion molecules was demonstrated by immunohistochemistry using monoclonal antibodies against VCAM-1, ICAM-1 and ELAM. And in situ hybriditation against ICAM-1 was also performed. The endothelial adhesion molecules, VCAM and ICAM, were expressed after 6 hours postinfection, respectively, and their expressions lasted for 72 hours. Similar expression of VCAM and ICAM appeared on endothelial cells by infection with virus, but the expression of ELAM was not recognized up to 72 hours postinfection. Microscopically, it was noted that many monocuclear cells adhered on endothelial cells infected with viruses. In an electronmicroscopic study, the transendothelial migration of mononuclear cells was observed on monolayered endothelial cells infected with virus. This results suggested that the endothelial adhesion molecules, particulary VCAM and ICAM, might be expressed on endothelial cells by infection with Hantaan virus and these molecules play a key role in the adhesion and extravasation of inflammatory cells around blood vessels.
Respiratory syncytial virus (RSV) infection is recognized by the innate immune system through Toll like receptors (TLRs) and retinoic acid inducible gene I. These pathways lead to the activation of type I interferons and resistance to infection. In contrast to TLRs, very few studies have examined the role of NOD-like receptors in viral recognition and induction of adaptive immune responses to RSV. Caspase-1 plays an essential role in the immune response via the maturation of the proinflammatory cytokines IL-$1{\beta}$ and IL-18. However, the role of caspase-1 in RSV infection in vivo is unknown. We demonstrate that RSV infection induces IL-$1{\beta}$ secretion and that caspase-1 deficiency in bone marrow derived dendritic cells leads to defective IL-$1{\beta}$ production, while normal RSV viral clearance and T cell responses are observed in caspase-1 deficient mice following respiratory infection with RSV. The frequencies of IFN-${\gamma}$ producing or RSV specific T cells in lungs from caspase-1 deficient mice are not impaired. In addition, we demonstrate that caspase-1 deficient neonatal or young mice also exhibit normal immune responses. Furthermore, we find that IL-1R deficient mice infected with RSV exhibit normal Th1 and cytotoxic T lymphocytes (CTL) immune responses. Collectively, these results demonstrate that in contrast to TLR pathways, caspase-1 might not play a central role in the induction of Th1 and CTL immune responses to RSV.
Purpose: Synthesis of regulated on activation, normal T-cells expressed and secreted (RANTES) in the airway has previously been shown to be elevated after respiratory syncytial virus (RSV) infection. However, since few studies have examined whether RSV-infected asthma patients express a higher level of RANTES than do normal individuals, we used a murine model of asthma to address this question. Methods: We prepared Dermatophagoides farinae-sensitized mice as an asthma model, and then infected them with RSV and analyzed the changes in airway responsiveness and the cell populations and cytokine levels of bronchoalveolar lavage fluid. Results: RANTES synthesis increased in response to RSV infection in both control mice and in asthma model (D. farinae) mice. However, there was no significant difference in the amount of RANTES produced following RSV infection between control and D. farinae mice. RSV infection affected neither interferon-${\gamma}$ synthesis nor airway responsiveness in either control or D. farinae mice. Conclusion: RSV infection did not induce more RANTES in a murine model of asthma than in control mice.
Journal of the Korean Association of Oral and Maxillofacial Surgeons
/
v.41
no.5
/
pp.251-258
/
2015
Objectives: This study was performed to evaluate the impact of glycosylated hemoglobin (HbA1c) level on characteristics and prognosis of maxillofacial fascial infection in diabetic patients. Materials and Methods: We reviewed the medical records of 72 patients (35 patients with HbA1c lower than 7.0% and 37 patients with HbA1c higher than 7.0%) diagnosed with maxillofacial fascial space infection and hospitalized for treatment at the Department of Oral and Maxillofacial Surgery in Dankook University Hospital (Cheonan, Korea) from January 2005 to February 2014. We compared demographics, parameters of glucoregulation (HbA1c), laboratory parameters of inflammation (white blood cell [WBC], C-reactive protein [CRP] count), type and number of involved spaces, type and number of antibiotics, period of hospitalization, number of surgical operations, need for tracheostomy, complications, computed tomography (CT), and microorganisms between the two groups. Results: Compared with the well-controlled diabetes mellitus (DM) group (HbA1c <7.0%), patients in the poorly-controlled (HbA1c ${\geq}7.0%$) DM group had the following characteristics: longer hospitalization periods, higher values of laboratory parameters of inflammation (WBC, CRP count) at the time of admission, higher number of antibiotics prescribed, more frequent complications, frequent deep neck space involvement, and distinctive main causative microorganisms. As the HbA1c level increases, hospitalization periods and incidence of complications increase gradually. Conclusion: This retrospective study suggests that regulation of DM significantly impacts maxillofacial fascial infection. Poorly controlled DM with high HbA1c level negatively influences the prognosis of infection.
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