Herath C.,Veterinary Vaccine Production Center |
Singh M.,Indian Veterinary Research Institute |
Kumar D.,Center for Immunology and Microbial Disease |
Ramakrishnan S.,Indian Veterinary Research Institute |
And 3 more authors.
Vaccine | Year: 2010
Fowl cholera is a serious problem in large and small scale poultry production. The present study describes the development and testing of an inactivated whole-cell, low-cost, safe, and effective vaccine for fowl cholera based on a previous work (Vaccine 23:5590-5598). Pasteurella multocida A: 1 grown in the presence of low FeCl3 concentrations, inactivated with higher concentrations of FeCl3, and adjuvanted with bacterial DNA from P. multocida B: 2 containing immunostimulatory CpG motifs protect chickens with a lethal P. multocida A: 1 challenge. Chickens were immunized with two whole-cell inactivated vaccine doses at 4 weeks apart and challenged 4 weeks after booster immunization. Experimental vaccines were pure, easy injectable, and caused very little distress in chickens due to their aqueous consistency. Vaccines and bacterial DNA (bDNA) posed no safety problems when chickens were injected subcutaneously (s.c.) with a single, double, and overdose of these preparations. Immunized chickens produced systemic IgY antibodies (Ab) responses and vaccine adjuvanted with bDNA protected 100% chickens from lethal intrapertoneal (i.p.) P. multocida A: 1 challenge. This work suggests that use of bDNA as an adjuvant can improve the cost-effectiveness of inactivated veterinary vaccines for their use in developing countries. Our future studies will focus on safety and potency evaluation of experimental and current vaccines using bDNA as an adjuvant. © 2010 Elsevier Ltd. All rights reserved.
Lin C.,Ordway Research Institute |
Crawford D.R.,Center for Immunology and Microbial Disease |
Lin S.,Ordway Research Institute |
Hwang J.,Academia Sinica, Taiwan |
And 10 more authors.
Carcinogenesis | Year: 2011
Resveratrol is a naturally occurring trihydroxyl-diphenylethylene compound that has been shown experimentally to have beneficial effects in the treatment of cancer and cardiovascular disease. Resveratrol induces programmed cell death (apoptosis) in these cells and activates important signal transducing proteins including extracellular signal-regulated kinases (ERKs) 1 and 2 in cancer cells. Resveratrol also causes nuclear accumulation of the enzyme cyclooxygenase (COX)-2 and of the oncogene suppressor protein, p53. We have studied the molecular basis of the anticancer actions of resveratrol using human ovarian carcinoma (OVCAR-3) cells. Our findings include the following: (i) nuclear accumulation of COX-2 in resveratrol-treated cells is blocked by the ERK1/2 inhibitor, PD98059; (ii) an inhibitor of COX-2 activity, NS398, prevents accumulation of ERK1/2, COX-2, activated p53 and small ubiquitin-like modifier (SUMO-1) in the nucleus; (iii) apoptosis, quantitated by nucleosome enzyme-linked immunosorbent assay and the nuclear abundance of the pro-apoptotic protein, BcL-xs, were inhibited by NS398. This finding implicates nuclear COX-2 in p53-mediated apoptosis induced by resveratrol. Sumoylation is important to stabilization of p53 and a COX-2-SUMO-1 interaction suggests sumoylation of COX-2 in resveratrol-treated cells and (iv) chromatin immunoprecipitation studies showed binding of induced nuclear COX-2 to the promoter region of PIG3 and Bax, pro-apoptotic gene targets of transcriptionally active p53. Nuclear accumulation of activated ERK1/2 and sumolyated COX-2 are essential to resveratrolinduced pSer-15-p53-mediated apoptosis in human ovarian cancer cells. © The Author 2010.Published by Oxford University Press. All rights reserved.
Andzinski L.,Molecular ImmunologyHelmholtz Center for Infection ResearchBraunschweig Germany |
Spanier J.,Helmholtz Center for Infection Research |
Kasnitz N.,Molecular ImmunologyHelmholtz Center for Infection ResearchBraunschweig Germany |
Kroger A.,Institute of Medical Microbiology |
And 6 more authors.
International Journal of Cancer | Year: 2016
The importance of endogenous Type I IFNs in cancer immune surveillance is well established by now. Their role in polarization of tumor-associated neutrophilic granulocytes into anti-tumor effector cells has been recently demonstrated. Yet, the cellular source of Type I IFNs as well as the mode of induction is not clearly defined. Here, we demonstrate that IFN-β is induced by growing murine tumors. Induction is mainly mediated via STING-dependent signaling pathways, suggesting tumor derived DNA as trigger. Transcription factors IRF3 and IRF5 were activated under these conditions which is consistent with tumor infiltrating dendritic cells (DCs) being the major cellular source of IFN-β at the tumor site. Besides DCs, tumor cells themselves are induced to contribute to the production of IFN-β. Taken together, our data provide further information on immune surveillance by Type I IFNs and suggest novel potent cellular targets for future cancer therapy. © 2016 UICC.
Zhang Y.,New York State Department of Health |
Zhang Y.,Albany State University |
Zhang Y.,Center for Immunology and Microbial Disease |
Gao D.,New York State Department of Health |
And 8 more authors.
Journal of Neuroimmunology | Year: 2013
Autism spectrum disorders (ASD) are neurodevelopmental disorders with unknown etiology. BTBR-T+tf/J (BTBR) mice, a mouse strain with behaviors that resemble autism and with elevated levels of anti-brain antibodies (Abs), have enhanced activation of peripheral B cells and CD4+ T cells and an expanded percentage of CD4+ T cells expressing Vβ6 chains. The CD4+CD25+Vβ6+ and Vβ6-splenic cells of BTBR mice have elevated levels of IL-4, IFN-γ and IL-17, but there appears to be no preferential CD4+ T subset skewing/polarization. The high level of IgG production by BTBR B cells was dependent on T cells from BTBR mice. The CD4+ T cells of BTBR mice, especially those expressing Vβ6 become spontaneously activated and expanded in an autoimmune-like manner, which occurred in both BTBR and B6 hosts that received an equal number of BTBR and B6 bone marrow cells. BTBR mice also have an elevated percentage of peripheral blood neutrophils, which may represent their elevated inflammatory state. B6 offspring derived from B6 dams that were gestationally injected with purified IgG from sera of BTBR mice, but not IgG of B6 mice, developed significantly impaired social behavior. Additionally, B6 offspring that developed in BTBR dams had impaired social behavior, while BTBR offspring that developed in B6 dams had improved social behavior. All of the immunological and behavioral parameters of BTBR mice were compared with those of B6 mice, which have relatively normal behaviors. The results indicate maternal Abs and possibly other maternal influences affect the social behavior of offspring. © 2013 Elsevier B.V.
Califano D.,Center for Immunology and Microbial Disease |
Cho J.J.,Center for Immunology and Microbial Disease |
Cho J.J.,University of Florida |
Uddin M.N.,Center for Immunology and Microbial Disease |
And 8 more authors.
Immunity | Year: 2015
Type 2 innate lymphoid cells (ILC2s) promote anti-helminth responses and contribute to allergies. Here, we report that Bcl11b, previously considered a T-cell-specific transcription factor, acted directly upstream of the key ILC2 transcription factor Gfi1 to maintain its expression in mature ILC2s. Consequently, Bcl11b-/- ILC2s downregulated Gata3 and downstream genes, including Il1rl1 (encoding IL-33 receptor), and upregulated Rorc and type 3 ILC (ILC3) genes. Additionally, independent of Gfi1, Bcl11b directly repressed expression of the gene encoding the ILC3 transcription factor Ahr, further contributing to silencing of ILC3 genes in ILC2s. Thus, Bcl11b-/- ILC2s lost their functions and gained ILC3 functions, and although they expanded in response to the protease allergen papain, they produced ILC3 but not ILC2 cytokines and caused increased airway infiltration of neutrophils instead of eosinophils. Our results demonstrate that Bcl11b is more than just a T-cell-only transcription factor and establish that Bcl11b sustains mature ILC2 genetic and functional programs and lineage fidelity. Regulation of mature innate lymphoid cell identity and function is poorly understood. Avram and colleagues demonstrate that Bcl11b, a transcription factor previously considered specific to T cells, sustains key ILC2 transcription factors and restricts essential ILC3 transcription factors in mature ILC2s, thus maintaining the genetic and functional programs of peripheral ILC2s. © 2015 Elsevier Inc.