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- Delaney, Joseph R, et al.
(författare)
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Cooperative control of Drosophila immune responses by the JNK and NF-kappaB signaling pathways.
- 2006
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Ingår i: EMBO Journal. - : Wiley. - 0261-4189 .- 1460-2075. ; 25:13, s. 3068-77
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Tidskriftsartikel (refereegranskat)abstract
- Jun N-terminal kinase (JNK) signaling is a highly conserved pathway that controls both cytoskeletal remodeling and transcriptional regulation in response to a wide variety of signals. Despite the importance of JNK in the mammalian immune response, and various suggestions of its importance in Drosophila immunity, the actual contribution of JNK signaling in the Drosophila immune response has been unclear. Drosophila TAK1 has been implicated in the NF-kappaB/Relish-mediated activation of antimicrobial peptide genes. However, we demonstrate that Relish activation is intact in dTAK1 mutant animals, and that the immune response in these mutant animals was rescued by overexpression of a downstream JNKK. The expression of a JNK inhibitor and induction of JNK loss-of-function clones in immune responsive tissue revealed a general requirement for JNK signaling in the expression of antimicrobial peptides. Our data indicate that dTAK1 is not required for Relish activation, but instead is required in JNK signaling for antimicrobial peptide gene expression.
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| 4. |
- Eneslätt, Kjell, et al.
(författare)
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Persistence of cell-mediated immunity three decades after vaccination with the live vaccine strain of Francisella tularensis
- 2011
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Ingår i: European Journal of Immunology. - Weinheim : Wiley-VCH Verlagsgesellschaft. - 0014-2980 .- 1521-4141. ; 41:4, s. 974-980
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Tidskriftsartikel (refereegranskat)abstract
- The efficacy of many vaccines against intracellular bacteria depends on the generation of cell-mediated immunity, but studies to determine the duration of immunity are usually confounded by re-exposure. The causative agent of tularemia, Francisella tularensis, is rare in most areas and, therefore, tularemia vaccination is an interesting model for studies of the longevity of vaccine-induced cell-mediated immunity. Here, lymphocyte proliferation and cytokine production in response to F. tularensis were assayed in two groups of 16 individuals, vaccinated 1-3 or 27-34 years previously. As compared to naïve individuals, vaccinees of both groups showed higher proliferative responses and, out of 17 cytokines assayed, higher levels of MIP-1β, IFN-γ, IL-10, and IL-5 in response to recall stimulation. The responses were very similar in the two groups of vaccinees. A statistical model was developed to predict the immune status of the individuals and by use of two parameters, proliferative responses and levels of IFN-γ, 91.1% of the individuals were correctly classified. Using flow cytometry analysis, we demonstrated that during recall stimulation, expression of IFN-γ by CD4(+) CCR7(+) , CD4(+) CD62L(+) , CD8(+) CCR7(+) , and CD8(+) CD62L(+) cells significantly increased in samples from vaccinated donors. In conclusion, cell-mediated immunity was found to persist three decades after tularemia vaccination without evidence of decline.
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| 5. |
- Eneslätt, Kjell, et al.
(författare)
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Signatures of T cells as correlates of immunity to Francisella tularensis
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:3, s. e32367-
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Tidskriftsartikel (refereegranskat)abstract
- Tularemia or vaccination with the live vaccine strain (LVS) of Francisella tularensis confers long-lived cell-mediated immunity. We hypothesized that this immunity depends on polyfunctional memory T cells, i.e., CD4(+) and/or CD8(+) T cells with the capability to simultaneously express several functional markers. Multiparametric flow cytometry, measurement of secreted cytokines, and analysis of lymphocyte proliferation were used to characterize in vitro recall responses of peripheral blood mononuclear cells (PBMC) to killed F. tularensis antigens from the LVS or Schu S4 strains. PBMC responses were compared between individuals who had contracted tularemia, had been vaccinated, or had not been exposed to F. tularensis (naive). Significant differences were detected between either of the immune donor groups and naive individuals for secreted levels of IL-5, IL-6, IL-10, IL-12, IL-13, IFN-gamma, MCP-1, and MIP-1 beta. Expression of IFN-gamma, MIP-1 beta, and CD107a by CD4(+)CD45RO(+) or CD8(+) CD45RO(+) T cells correlated to antigen concentrations. In particular, IFN-gamma and MIP-1 beta strongly discriminated between immune and naive individuals. Only one cytokine, IL-6, discriminated between the two groups of immune individuals. Notably, IL-2- or TNF-alpha-secretion was low. Our results identify functional signatures of T cells that may serve as correlates of immunity and protection against F. tularensis.
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- Ertürk-Hasdemir, Deniz, et al.
(författare)
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Two roles for the Drosophila IKK complex in the activation of Relish and the induction of antimicrobial peptide genes
- 2009
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 106:24, s. 9779-9784
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Tidskriftsartikel (refereegranskat)abstract
- The Drosophila NF-kappa B transcription factor Relish is an essential regulator of antimicrobial peptide gene induction after Gram-negative bacterial infection. Relish is a bipartite NF-kappa B precursor protein, with an N-terminal Rel homology domain and a C-terminal I kappa B-like domain, similar to mammalian p100 and p105. Unlike these mammalian homologs, Relish is endoproteolytically cleaved after infection, allowing the N-terminal NF-kappa B module to translocate to the nucleus. Signal-dependent activation of Relish, including cleavage, requires both the Drosophila I kappa B kinase (IKK) and death-related ced-3/Nedd2-like protein (DREDD), the Drosophila caspase-8 like protease. In this report, we show that the IKK complex controls Relish by direct phosphorylation on serines 528 and 529. Surprisingly, these phosphorylation sites are not required for Relish cleavage, nuclear translocation, or DNA binding. Instead they are critical for recruitment of RNA polymerase II and antimicrobial peptide gene induction, whereas IKK functions noncatalytically to support Dredd-mediated cleavage of Relish.
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| 7. |
- Kinsman, John, et al.
(författare)
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Good practices and challenges in addressing poliomyelitis and measles in the European Union
- 2018
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Ingår i: European Journal of Public Health. - : Oxford University Press. - 1101-1262 .- 1464-360X. ; 28:4, s. 730-734
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Tidskriftsartikel (refereegranskat)abstract
- Background: All European Union (EU) and European Economic Area (EEA) Member States have pledged to ensure political commitment towards sustaining the region's poliomyelitis-free status and eliminating measles. However, there remain significant gaps between policy and practice in many countries. This article reports on an assessment conducted for the European Commission that aimed to support improvements in preparedness and response to poliomyelitis and measles in Europe.Methods: A documentary review was complemented by qualitative interviews with professionals working in International and EU agencies, and in at-risk or recently affected EU/EEA Member States (six each for poliomyelitis and measles). Twenty-six interviews were conducted on poliomyelitis and 24 on measles; the data were subjected to thematic analysis. Preliminary findings were then discussed at a Consensus Workshop with 22 of the interviewees and eight other experts.Results: Generic or disease-specific plans exist in the participating countries and cross-border communications during outbreaks were generally reported as satisfactory. However, surveillance systems are of uneven quality, and clinical expertise for the two diseases is limited by a lack of experience. Serious breaches of protocol have recently been reported from companies producing poliomyelitis vaccines, and vaccine coverage rates for both diseases were also sub-optimal. A set of suggested good practices to address these and other challenges is presented.Conclusions: Poliomyelitis and measles should be brought fully onto the policy agendas of all EU/EEA Member States, and adequate resources provided to address them. Each country must abide by the relevant commitments that they have already made.
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| 8. |
- Kleino, Anni, et al.
(författare)
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Inhibitor of apoptosis 2 and TAK1-binding protein are components of the Drosophila Imd pathway.
- 2005
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Ingår i: EMBO J. - 0261-4189. ; 24:19, s. 3423-34
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Tidskriftsartikel (refereegranskat)abstract
- The Imd signaling cascade, similar to the mammalian TNF-receptor pathway, controls antimicrobial peptide expression in Drosophila. We performed a large-scale RNAi screen to identify novel components of the Imd pathway in Drosophila S2 cells. In all, 6713 dsRNAs from an S2 cell-derived cDNA library were analyzed for their effect on Attacin promoter activity in response to Escherichia coli. We identified seven gene products required for the Attacin response in vitro, including two novel Imd pathway components: inhibitor of apoptosis 2 (Iap2) and transforming growth factor-activated kinase 1 (TAK1)-binding protein (TAB). Iap2 is required for antimicrobial peptide response also by the fat body in vivo. Both these factors function downstream of Imd. Neither TAB nor Iap2 is required for Relish cleavage, but may be involved in Relish nuclear localization in vitro, suggesting a novel mode of regulation of the Imd pathway. Our results show that an RNAi-based approach is suitable to identify genes in conserved signaling cascades.
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| 9. |
- Lindmark, H, et al.
(författare)
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Enteric bacteria counteract lipopolysaccharide induction of antimicrobial peptide genes.
- 2001
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Ingår i: J Immunol. - 0022-1767. ; 167, s. 6920-6923
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Tidskriftsartikel (refereegranskat)abstract
- The humoral immunity of Drosophila involves the production of antimicrobial peptides, which are induced by evolutionary conserved microbial molecules, like LPS. By using Drosophila mbn-2 cells, we found that live bacteria, including E. coli, Salmonella typhimurium, Erwinia carotovora, and Pseudomonas aeruginosa, prevented LPS from inducing antimicrobial peptide genes, while Micrococcus luteus and Streptococcus equi did not. The inhibitory effect was seen at bacterial levels from 20 per mbn-2 cell, while antimicrobial peptides were induced at lower bacterial concentrations (< or =2 bacteria per cell) also in the absence of added LPS. Gel shift experiment suggests that the inhibitory effect is upstream or at the level of the activation of the transcription factor Relish, a member of the NF-kappaB/Rel family. The bacteria have to be in physical contact with the cells, but not phagocytosed, to prevent LPS induction. Interestingly, the inhibiting mechanism is, at least for E. coli, independent of the type III secretion system, indicating that the inhibitory mechanism is unrelated to the one earlier described for YopJ from Yersinia.
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| 10. |
- Plamboeck, Agneta H., et al.
(författare)
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Laboratory analysis of CBRN-substances : Stakeholder networks as clue to higher CBRN resilience in Europe
- 2016
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Ingår i: TrAC. Trends in analytical chemistry. - : Elsevier BV. - 0165-9936 .- 1879-3142. ; 85:Part B, s. 2-9
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Tidskriftsartikel (refereegranskat)abstract
- The threat of terrorists using CBRN agents continues to pose a risk of mass casualties and severe disruption of societal functions in Europe. Standardisation of crisis management activities is one important step towards effective national and international interoperability and increased resilience. Understanding which CBRN agents are involved in an incident is vital for appropriate response measures. We applied a system's view on the process of CBRN sample analysis and see three discrete applications; Immediate incident response, Forensics, Post incident monitoring. Together with laboratory experts and policy makers from across Europe we identified needs for quality assurance measures in these three areas. Here, we suggest various harmonisation activities that can facilitate interoperability between all stakeholders concerned with CBRN sample analysis. Foremost, we recommend purpose-oriented laboratory networks, but also minimum performance requirements for First Responders' detection and sampling capabilities, best practices for sample transport and documentation.
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