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Coabitação com um parceiro doente: conseqüências sobre o comportamento, a atividade imune inata e o crescimento tumoral; Cohabiting with a sick mate: consequences on behavior, innate immune activity, and tumor growht

Alves, Glaucie Jussilane
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 16/08/2005 PT
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A atividade do sistema nervoso central (SNC) afeta aquela do sistema imune e esta por sua vez, através de produtos originados em células imunes, como por exemplo, as citocinas modificam a atividade cerebral e, portanto, alguns comportamentos. O ato de conviver com pessoas portadoras de um tumor ou de patologias crônicas debilitantes tem sido estudado por vários pesquisadores, os quais têm relatado evidencias que mostram ser algumas condições psicológicas experimentadas por ?caregivers? associadas com variações de comportamento e de imunidade. Manifestações de estresse têm sido intensamente estudadas nestas pessoas. Neste sentido, e guardado os devidos cuidados com as extrapolações, não existe um modelo animal especificamente desenvolvido para analisar, em laboratório, as eventuais alterações imunes que possam ocorrer em animais que convivem com um outro doente. Este foi o objeto do presente trabalho. Mais especificamente, avaliou-se a existência de uma possível interação neuroimune em camundongas que coabitaram com outras portadoras de um tumor de Ehrlich, através da análise de parâmetros hematológicos, imunológicos, hormonais, comportamentais e neuroquímicos. Os resultados obtidos mostraram que a convivência por 11 dias com um animal portador do tumor de Ehrlich produziu em camundongas: 1) leucopenia; 2) diminuição do burst oxidativo induzido por PMA e por S. aureus e da porcentagem e...

Estudo da imunidade inata na rosácea: células de Langerhans, células dentríncas pasmocitóides, receptores toll-like e expressão da forma induzida da enzima óxido nítrico sintase em biópsias de pele; Inate immunity in rosacea: Langerhans cells, plasmacytoid dentritic cells, toll-like receptors and inducible oxide nitric synthase (iNOS) expression in skin specimens

Moura, Ana Karina Alves
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 22/02/2013 PT
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Introdução: Rosácea é uma doença inflamatória cutânea crônica relativamente comum, com incidência que varia de 2 a 10%. Caracteriza-se pelo surgimento de pápulas e pápulo-pustulas, eritema e telangiectasias precedidas por episódios de flushing. Apesar de não ser doença que comprometa o estado geral dos doentes, por ter acometimento preferencial da face, representa problema estético acentuado que interfere na socialização e qualidade de vida dos doentes. A etiologia da rosácea permanece incerta. A participação da imunidade inata tem sido implicada recentemente. Objetivo: Este estudo avaliou o envolvimento da imunidade inata na patogenia da rosácea através de pesquisa de células de Langerhans, células plasmocitóides (PDC), receptores "toll-like" (TLR) e expressão da forma induzida da enzima óxido nítrico sintase (iNOS) em biopsias de pele de pacientes com diagnóstico de rosácea. Métodos: Biopsias de 28 pacientes com diagnóstico clínico e histopatológico de Rosácea foram classificadas de acordo com características histopatológicas em Rosácea Granulomatosa (RG) (n = 10) e Rosácea Não Granulomatosa (RNG) (n = 18), e submetidas à técnica imunoistoquímica para demonstração de células de Langerhans (anticorpo anti-CD1a) (n = 26)...

Avaliação da resposta inflamatória e da resposta imune inata na célula apresentadora de antígeno em recém-nascidos de termo sepse tardia; Inflammatory and innate immune response in antigen-presenting cell from term newborn with late onset sepsis

Redondo, Ana Carolina Costa
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 25/11/2013 PT
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473.34008%
INTRODUÇÃO: Apesar do contínuo progresso no tratamento e suporte clínico a sepse continua sendo uma das principais causas de morbidade e mortalidade nas unidades de terapia intensiva, com desfechos semelhantes ao longo dos últimos 50 anos. A suscetibilidade à infecção grave no recém-nascido é parcialmente devida à imaturidade do sistema imune inato associado à mínima em exposição antigênica in utero e à ação ineficaz das células T efetoras e das célula B. Embora a ativação do sistema imune inato por padrões de reconhecimento (PRR) como os dos receptores Toll-like (TLR) tenham sua importância amplamente reconhecida nos últimos anos, seu comportamento frente a uma infecção in vivo ainda não foi completamente compreendido. Neste trabalho nós analisamos a expressão dos TLR-2 e TLR-4 em células apresentadoras de antígeno em recém-nascidos com e sem sepse. CAUSUÍSTICA E MÉTODO: Trata-se de um estudo prospectivo realizado no período entre fevereiro de 2011 e janeiro de 2013 onde foram incluídos quarenta e cinco recém-nascidos a termo, sem malformação congênita, admitidos na Unidade de Cuidados Intensivos Neonatal do Instituto da Criança-HCFMUSP e divididos em grupos 1 e 2. O grupo 1 consistiu em 27 recém-nascidos com diagnóstico clínico e laboratorial de sepse tardia enquanto que o grupo 2 foi composto por 18 recém-nascidos sem quadro séptico vigente. As citocinas foram determinadas por teste de CBA em sangue periférico. A expressão e MFI dos TLR-2 e TLR-4 foi determinado por imunofenotipagem em APCs e linfócitos no sangue periférico total através de análise pelo citômetro de fluxo BD FACSDiva. RESULTADOS: Os dados clínicos foram semelhantes entre os grupos 1 e 2...

Immunity in plants and animals: common ends through different means using similar tools

Menezes, H.; Jared, C.
Fonte: Elsevier B.V. Publicador: Elsevier B.V.
Tipo: Artigo de Revista Científica Formato: 1-7
ENG
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A comparative approach is potentially useful for understanding the role of mammal innate immunity role in stimulating adaptive immunity as well as the relationship between these two types of immune strategies. Considerable progress has been made in the elucidation of the co-ordinated events involved in plant perception of infection and their mobilisation of defence responses. Although lacking immunoglobulin molecules, circulating cells, and phagocytic processes, plants successfully use pre-formed physical and chemical innate defences, as well as inducible adaptive immune strategies. In the present paper, we review some shared and divergent immune aspects present in both animals and plants. (C) 2002 Elsevier B.V. All rights reserved.

Role of TLR-2 and fungal surface antigens on innate immune response against Sporothrix schenckii

Negrini, Thais de C.; Ferreira, Lucas S.; Alegranci, Pâmela; Arthur, Rodrigo A.; Sundfeld, Pedro P.; Maia, Danielle C. G.; Spolidorio, Luis C.; Carlos, Iracilda Z.
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 36-48
ENG
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Sporotrichosis is an infection caused by the dimorphic fungus Sporothrix schenckii. Toll-like receptors (TLRs) play an important role in immunity, since they bind to pathogen surface antigens and initiate the immune response. However, little is known about the role of TLR-2 and fungal surface antigens in the recognition of S. schenckii and in the subsequent immune response. This study aimed to evaluate the involvement of TLR-2 and fungal surface soluble (SolAg) and lipidic (LipAg) antigens in phagocytosis of S. schenckii and production of immune mediators by macrophages obtained from WT and TLR-2 -/- animals. The results showed that TLR-2-/- animals had had statistical lower percentage of macrophages with internalized yeasts compared to WT. SolAg and LipAg impaired phagocytosis and immunological mediator production for both WT and TLR-2-/-. The absence of TLR-2 led to lower production of the cytokines TNF, IL-1β, IL-12 and IL-10 compared to WT animals. These results suggest a new insight in relation to how the immune system, through TLR-2, recognizes and induces the production of mediators in response to the fungus S. schenckii. Copyright © Informa Healthcare USA, Inc.

Expression and Putative Function of Innate Immunity Genes under In Situ Conditions in the Symbiotic Hydrothermal Vent Tubeworm Ridgeia piscesae

Nyholm, Spencer V.; Song, Pengfei; Dang, Jeanne; Bunce, Corey; Girguis, Peter R.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
EN_US
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The relationships between hydrothermal vent tubeworms and sulfide-oxidizing bacteria have served as model associations for understanding chemoautotrophy and endosymbiosis. Numerous studies have focused on the physiological and biochemical adaptations that enable these symbioses to sustain some of the highest recorded carbon fixation rates ever measured. However, far fewer studies have explored the molecular mechanisms underlying the regulation of host and symbiont interactions, specifically those mediated by the innate immune system of the host. To that end, we conducted a series of studies where we maintained the tubeworm, Ridgeia piscesae, in high-pressure aquaria and examined global and quantitative changes in gene expression via high-throughput transcriptomics and quantitative real-time PCR (qPCR). We analyzed over 32,000 full-length expressed sequence tags as well as 26 Mb of transcript sequences from the trophosome (the organ that houses the endosymbiotic bacteria) and the plume (the gas exchange organ in contact with the free-living microbial community). R. piscesae maintained under conditions that promote chemoautotrophy expressed a number of putative cell signaling and innate immunity genes, including pattern recognition receptors (PRRs)...

A Neonatal Model of Intravenous Staphylococcus epidermidis Infection in Mice <24 h Old Enables Characterization of Early Innate Immune Responses

Kronforst, Kenny D.; Mancuso, Christy J.; Power Coombs, Melanie R.; Stevens, Chad; Otto, Michael; Mallard, Carina; Wang, Xiaoyang; Pettengill, Matthew A; Ninkovic, Jana; Goldmann, Donald Alan; Levy, Ofer
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
EN_US
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Staphylococcus epidermidis (SE) causes late onset sepsis and significant morbidity in catheterized preterm newborns. Animal models of SE infection are useful in characterizing disease mechanisms and are an important approach to developing improved diagnostics and therapeutics. Current murine models of neonatal bacterial infection employ intraperitoneal or subcutaneous routes at several days of age, and may, therefore, not accurately reflect distinct features of innate immune responses to bacteremia. In this study we developed, validated, and characterized a murine model of intravenous (IV) infection in neonatal mice <24 hours (h) old to describe the early innate immune response to SE. C57BL/6 mice <24 h old were injected IV with 106, 107, 108 colony-forming units (CFU) of SE 1457, a clinical isolate from a central catheter infection. A prospective injection scoring system was developed and validated, with only high quality injections analyzed. Newborn mice were euthanized between 2 and 48 h post-injection and spleen, liver, and blood collected to assess bacterial viability, gene expression, and cytokine production. High quality IV injections demonstrated inoculum-dependent infection of spleen, liver and blood. Within 2 h of injection...

NEMO Binds Ubiquitinated TANK-Binding Kinase 1 (TBK1) to Regulate Innate Immune Responses to RNA Viruses

Li, Shitao; Dorf, Martin Edward; Wang, Lingyan
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
EN_US
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RIG-I-like receptors (RLR) are intracellular sensors utilized by nearly all cell types for recognition of viral RNA, initiation of antiviral defense, and induction of type I interferons (IFN). TBK1 is a critical kinase implicated in RLR-dependent IFN transcription. Posttranslational modification of TBK1 by K63-linked ubiquitin is required for RLR driven signaling. However, the TBK1 ubiquitin acceptor sites and the function of ubiquitinated TBK1 in the signaling cascade are unknown. We now show that TBK1 is ubiquitinated on residues K69, K154, and K372 in response to infection with RNA virus. The K69 and K154 residues are critical for innate antiviral responses and IFN production. Ubiquitinated TBK1 recruits the downstream adaptor NEMO through ubiquitin binding domains. The assembly of the NEMO/TBK1 complex on the mitochondrial protein MAVS leads to activation of TBK1 kinase activity and phosphorylation of the transcription factor, interferon response factor 3. The combined results refine current views of RLR signaling, define the role of TBK1 polyubiquitination, and detail the mechanisms involved in signalosome assembly.

Both innate immunity and type 1 humoral immunity to Streptococcus pneumoniae are mediated by MyD88 but differ in their relative levels of dependence on toll-like receptor 2

Khan, A.; Chen, Q.; Wu, Z.Q.; Paton, J.; Snapper, C.
Fonte: Amer Soc Microbiology Publicador: Amer Soc Microbiology
Tipo: Artigo de Revista Científica
Publicado em //2005 EN
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Little is known regarding the role of Toll-like receptors (TLRs) in regulating protein- and polysaccharide-specific immunoglobulin (Ig) isotype production in response to an in vivo challenge with an extracellular bacterium. In this report we demonstrate that MyD88–/–, but not TLR2–/–, mice are markedly defective in their induction of multiple splenic proinflammatory cytokine- and chemokine-specific mRNAs after intraperitoneal (i.p.) challenge with heat-killed Streptococcus pneumoniae capsular type 14 (S. pneumoniae type 14). This is correlated with analogous responses in splenic cytokine protein release in vitro following addition of S. pneumoniae type 14. Consistent with these data, naïve MyD88–/–, but not TLR2–/–, mice are more sensitive to killing following i.p. challenge with live S. pneumoniae type 14, relative to responses in wild-type mice. However, prior immunization of MyD88–/– mice with heat-killed S. pneumoniae type 14 protects against an otherwise-lethal challenge with live S. pneumoniae type 14. Surprisingly, both MyD88–/– and TLR2–/– mice exhibit striking and equivalent defects in elicitation of type 1 IgG isotypes (IgG3, IgG2b, and IgG2a), but not the type 2 IgG isotype, IgG1, specific for several protein and polysaccharide antigens...

The classical pathway is the dominant complement pathway required for innate immunity to Streptococcus pneumoniae infection in mice

Brown, J.; Hussell, T.; Gilliland, S.; Holden, D.; Paton, J.; Ehrenstein, M.; Walport, M.; Botto, M.
Fonte: Natl Acad Sciences Publicador: Natl Acad Sciences
Tipo: Artigo de Revista Científica
Publicado em //2002 EN
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The complement system is an important component of the innate immune response to bacterial pathogens, including Streptococcus pneumoniae. The classical complement pathway is activated by antibody–antigen complexes on the bacterial surface and has been considered predominately to be an effector of the adaptive immune response, whereas the alternative and mannose-binding lectin pathways are activated directly by bacterial cell surface components and are considered effectors of the innate immune response. Recently, a role has been suggested for the classical pathway during innate immunity that is activated by natural IgM or components of the acute-phase response bound to bacterial pathogens. However, the functional importance of the classical pathway for innate immunity to S. pneumoniae and other bacterial pathogens, and its relative contribution compared with the alternative and mannose-binding lectin pathways has not been defined. By using strains of mice with genetic deficiencies of complement components and secretory IgM we have investigated the role of each complement pathway and natural IgM for innate immunity to S. pneumoniae. Our results show that the proportion of a population of S. pneumoniae bound by C3 depends mainly on the classical pathway...

The role of complement in innate, adaptive and eosinophil-dependent immunity to the nematode Nippostrongylus brasiliensis

Giacomin, P.; Gordon, D.; Botto, M.; Daha, M.; Sanderson, S.; Taylor, S.; Dent, L.
Fonte: Pergamon-Elsevier Science Ltd Publicador: Pergamon-Elsevier Science Ltd
Tipo: Artigo de Revista Científica
Publicado em //2008 EN
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Complement may be important for immunity to infection with parasitic helminths, by promoting the recruitment of leukocytes to infected tissues and by modulating the function of cytotoxic effector leukocytes. However, the importance of complement in vivo during helminth infection is poorly understood. In this study, mice lacking classical (C1q-deficient), alternative (factor B-deficient) or all pathways of complement activation (C3-deficient) were used to assess the role of complement in immunity to the nematode Nippostrongylus brasiliensis. Double-mutant complement-deficient/IL-5 transgenic (Tg) mice were used to determine if complement is required for the strong eosinophil-dependent resistance to this parasite. Complement activation on larvae (C3 deposition), extracellular eosinophil peroxidase activity, larval aggregation and eosinophil recruitment to the skin 30 min post-injection (p.i.) of larvae were reduced in factor B-deficient mice. Inhibition of the C5a receptor with the antagonist PMX53 impaired eosinophil and neutrophil recruitment to the skin. C3 deposition on larvae was minimal by 150 min p.i. and at this time cell adherence, larval aggregation, eosinophil recruitment and degranulation were complement-independent. Factor B and C3 deficiency were associated with higher lung larval burdens in primary infections. Complement-deficient/IL-5 Tg mice were highly resistant to N. brasiliensis...

Innate transcriptional networks activated in bladder in response to uropathogenic Escherichia coli drive diverse biological pathways and rapid synthesis of IL-10 for defense against bacterial urinary tract Infection

Duell, B.; Carey, A.; Tan, C.; Cui, X.; Webb, R.; Totsika, M.; Schembri, M.; Derrington, P.; Irving-Rodgers, H.; Brooks, A.; Cripps, A.; Crowley, M.; Ulett, G.
Fonte: Amer Assoc Immunologists Publicador: Amer Assoc Immunologists
Tipo: Artigo de Revista Científica
Publicado em //2012 EN
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Early transcriptional activation events that occur in bladder immediately following bacterial urinary tract infection (UTI) are not well defined. In this study, we describe the whole bladder transcriptome of uropathogenic Escherichia coli (UPEC) cystitis in mice using genome-wide expression profiling to define the transcriptome of innate immune activation stemming from UPEC colonization of the bladder. Bladder RNA from female C57BL/6 mice, analyzed using 1.0 ST-Affymetrix microarrays, revealed extensive activation of diverse sets of innate immune response genes, including those that encode multiple IL-family members, receptors, metabolic regulators, MAPK activators, and lymphocyte signaling molecules. These were among 1564 genes differentially regulated at 2 h postinfection, highlighting a rapid and broad innate immune response to bladder colonization. Integrative systems-level analyses using InnateDB (http://www.innatedb.com) bioinformatics and ingenuity pathway analysis identified multiple distinct biological pathways in the bladder transcriptome with extensive involvement of lymphocyte signaling, cell cycle alterations, cytoskeletal, and metabolic changes. A key regulator of IL activity identified in the transcriptome was IL-10...

Innate immune recognition of poxviral vaccine vectors

Lousberg, E.; Diener, K.; Brown, M.; Hayball, J.
Fonte: Future Drugs Ltd. Publicador: Future Drugs Ltd.
Tipo: Artigo de Revista Científica
Publicado em //2011 EN
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The study of poxviruses pioneered the field of vaccinology after Jenner’s remarkable discovery that ‘vaccination’ with the phylogenetically related cowpox virus conferred immunity to the devastating disease of smallpox. The study of poxviruses continues to enrich the field of virology because the global eradication of smallpox provides a unique example of the potency of effective immunization. Other poxviruses have since been developed as vaccine vectors for clinical and veterinary applications and include modified vaccinia virus strains such as modified vaccinia Ankara and NYVAC as well as the avipox viruses, fowlpox virus and canarypox virus. Despite the empirical development of poxvirus-based vectored vaccines, it is only now becoming apparent that we need to better understand how the innate arm of the immune system drives adaptive immunity to poxviruses, and how this information is relevant to vaccine design strategies, which are the topics addressed in this article.; Erin L. Lousberg, Kerrilyn R. Diener, Michael P. Brown and John D. Hayball

Altered immunity and dendritic cell activity in the periphery of mice after long-term engraftment with bone marrow from ultraviolet-irradiated mice

Ng, R.; Scott, N.; Strickland, D.; Gorman, S.; Grimbaldeston, M.; Norval, M.; Waithman, J.; Hart, P.
Fonte: American Association of Immunologists Publicador: American Association of Immunologists
Tipo: Artigo de Revista Científica
Publicado em //2013 EN
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Alterations to dendritic cell (DC) progenitors in the bone marrow (BM) may contribute to long-lasting systemic immunosuppression (>28 d) following exposure of the skin of mice to erythemal UV radiation (UVR). DCs differentiated in vitro from the BM of mice 3 d after UVR (8 kJ/m2) have a reduced capacity to initiate immunity (both skin and airways) when adoptively transferred into naive mice. Studies in IL-10−/− mice suggested that UV-induced IL-10 was not significantly involved. To investigate the immune capabilities of peripheral tissue DCs generated in vivo from the BM of UV-irradiated mice, chimeric mice were established. Sixteen weeks after reconstitution, contact hypersensitivity responses were significantly reduced in mice reconstituted with BM from UV-irradiated mice (UV-chimeric). When the dorsal skin of UV-chimeric mice was challenged with innate inflammatory agents, the hypertrophy induced in the draining lymph nodes was minimal and significantly less than that measured in control-chimeric mice challenged with the same inflammatory agent. When DCs were differentiated from the BM of UV-chimeric mice using FLT3 ligand or GM-CSF + IL-4, the cells maintained a reduced priming ability. The diminished responses in UV-chimeric mice were not due to different numerical or proportional reconstitution of BM or the hematopoietic cells in blood...

Cutaneous immunosurveillance and regulation of inflammation by group 2 innate lymphoid cells

Roediger, B.; Kyle, R.; Yip, K.; Sumaria, N.; Guy, T.; Kim, B.; Mitchell, A.; Tay, S.; Jain, R.; Forbes-Blom, E.; Chen, X.; Tong, P.; Bolton, H.; Artis, D.; Paul, W.; Fazekas de St Groth, B.; Grimbaldeston, M.; Le Gros, G.; Weninger, W.
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em //2013 EN
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Type 2 immunity is critical for defense against cutaneous infections but also underlies the development of allergic skin diseases. We report the identification in normal mouse dermis of an abundant, phenotypically unique group 2 innate lymphoid cell (ILC2) subset that depended on interleukin 7 (IL-7) and constitutively produced IL-13. Intravital multiphoton microscopy showed that dermal ILC2 cells specifically interacted with mast cells, whose function was suppressed by IL-13. Treatment of mice deficient in recombination-activating gene 1 (Rag1−/−) with IL-2 resulted in the population expansion of activated, IL-5-producing dermal ILC2 cells, which led to spontaneous dermatitis characterized by eosinophil infiltrates and activated mast cells. Our data show that ILC2 cells have both pro- and anti-inflammatory properties and identify a previously unknown interactive pathway between two innate populations of cells of the immune system linked to type 2 immunity and allergic diseases.; Ben Roediger, Ryan Kyle, Kwok Ho Yip, Nital Sumaria, Thomas V Guy, Brian S Kim, Andrew J Mitchell, Szun S Tay, Rohit Jain, Elizabeth Forbes-Blom, Xi Chen, Philip L Tong, Holly A Bolton, David Artis, William E Paul, Barbara Fazekas de St Groth, Michele A Grimbaldeston...

Inhibition of RelA-Ser536 phosphorylation by a competing peptide reduces mouse liver fibrosis without blocking the innate immune response

Moles, A.; Sanchez, A.; Banks, P.; Murphy, L.; Luli, S.; Borthwick, L.; Fisher, A.; O'Reilly, S.; van Laar, J.; White, S.; Perkins, N.; Burt, A.; Mann, D.; Oakley, F.
Fonte: John Wiley & Sons Publicador: John Wiley & Sons
Tipo: Artigo de Revista Científica
Publicado em //2013 EN
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466.28383%
Phosphorylation of the RelA subunit at serine 536 (RelA-P-Ser536) is important for hepatic myofibroblast survival and is mechanistically implicated in liver fibrosis. Here, we show that a cell-permeable competing peptide (P6) functions as a specific targeted inhibitor of RelA-P-Ser536 in vivo and exerts an antifibrogenic effect in two progressive liver disease models, but does not impair hepatic inflammation or innate immune responses after lipopolysaccharide challenge. Using kinase assays and western blotting, we confirm that P6 is a substrate for the inhibitory kappa B kinases (IKKs), IKKα and IKKβ, and, in human hepatic myofibroblasts, P6 prevents RelA-P-Ser536, but does not affect IKK activation of IκBα. We demonstrate that RelA-P-Ser536 is a feature of human lung and skin fibroblasts, but not lung epithelial cells, in vitro and is present in sclerotic skin and diseased lungs of patients suffering from idiopathic pulmonary fibrosis. Conclusion: RelA-P-Ser536 may be a core fibrogenic regulator of fibroblast phenotype.; Anna Moles, Ana M. Sanchez, Paul S. Banks, Lindsay B. Murphy, Saimir Luli, Lee Borthwick, Andrew Fisher, Steven O'Reilly, Jacob M. van Laar, Steven A. White, Neil D. Perkins, Alastair D. Burt, Derek A. Mann and Fiona Oakley

Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjogren's syndrome

Lessard, C.; Rischmueller, M.
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em //2013 EN
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479.9674%
Sjögren's syndrome is a common autoimmune disease (affecting ∼0.7% of European Americans) that typically presents as keratoconjunctivitis sicca and xerostomia. Here we report results of a large-scale association study of Sjögren's syndrome. In addition to strong association within the human leukocyte antigen (HLA) region at 6p21 (Pmeta = 7.65 × 10(-114)), we establish associations with IRF5-TNPO3 (Pmeta = 2.73 × 10(-19)), STAT4 (Pmeta = 6.80 × 10(-15)), IL12A (Pmeta = 1.17 × 10(-10)), FAM167A-BLK (Pmeta = 4.97 × 10(-10)), DDX6-CXCR5 (Pmeta = 1.10 × 10(-8)) and TNIP1 (Pmeta = 3.30 × 10(-8)). We also observed suggestive associations (Pmeta < 5 × 10(-5)) with variants in 29 other regions, including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2 and PHIP, among others. These results highlight the importance of genes that are involved in both innate and adaptive immunity in Sjögren's syndrome.; Christopher J Lessard ... Maureen Rischmueller ... et al.

Sialyl Tn-Expressing Bladder Cancer Cells Induce a Tolerogenic Phenotype in Innate and Adaptive Immune Cells

Carrascal, M; Severino, P; Cabral, MG; Silva, M; Ferreira, JA; Calais da Silva, F; Quinto, H; Pen, C; Ligeiro, D; Lara Santos, L; Dall'Olio, F; Videira, P
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
Publicado em //2014 ENG
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Despite the wide acceptance that glycans are centrally implicated in immunity, exactly how they contribute to the tilt immune response remains poorly defined. In this study, we sought to evaluate the impact of the malignant phenotype-associated glycan, sialyl-Tn (STn) in the function of the key orchestrators of the immune response, the dendritic cells (DCs). In high grade bladder cancer tissue, the STn antigen is significantly overexpressed and correlated with the increased expression of ST6GALNAC1 sialyltransferase. Bladder cancer tissue presenting elevated expression of ST6GALNAC1 showed a correlation with increased expression of CD1a, a marker for bladder immature DCs and showed concomitant low levels of Th1-inducing cytokines IL-12 and TNF-α. In vitro, human DCs co-incubated with STn+ bladder cancer cells, had an immature phenotype (MHC-IIlow, CD80low and CD86low) and were unresponsive to further maturation stimuli. When contacting with STn+ cancer cells, DCs expressed significantly less IL-12 and TNF-α. Consistent with a tolerogenic DC profile, T cells that were primed by DCs pulsed with antigens derived from STn+ cancer cells were not activated and showed a FoxP3high IFN-γlow phenotype. Blockade of STn antigens and of STn+ glycoprotein...

On the Control of Acute Rodent Malaria Infections by Innate Immunity

Kochin, Beth F.; Yates, Andrew J.; de Roode, Jacobus C.; Antia, Rustom
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 06/05/2010 EN
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Does specific immunity, innate immunity or resource (red blood cell) limitation control the first peak of the blood-stage parasite in acute rodent malaria infections? Since mice deficient in specific immunity exhibit similar initial dynamics as wild-type mice it is generally viewed that the initial control of parasite is due to either limitation of resources (RBC) or innate immune responses. There are conflicting views on the roles of these two mechanisms as there is experimental evidence supporting both these hypotheses. While mathematical models based on RBC limitation are capable of describing the dynamics of primary infections, it was not clear whether a model incorporating the key features of innate immunity would be able to do the same. We examine the conditions under which a model incorporating parasite and innate immunity can describe data from acute Plasmodium chabaudi infections in mice. We find that innate immune response must decay slowly if the parasite density is to fall rather than equilibrate. Further, we show that within this framework the differences in the dynamics of two parasite strains are best ascribed to differences in susceptibility to innate immunity, rather than differences in the strains' growth rates or their propensity to elicit innate immunity. We suggest that further work is required to determine if innate immunity or resource limitation control acute malaria infections in mice.

Innate lymphoid cells and natural killer T cells in the gastrointestinal tract immune system

Montalvillo,Enrique; Garrote,José Antonio; Bernardo,David; Arranz,Eduardo
Fonte: Revista Española de Enfermedades Digestivas Publicador: Revista Española de Enfermedades Digestivas
Tipo: info:eu-repo/semantics/article; journal article; info:eu-repo/semantics/publishedVersion Formato: text/html; application/pdf
Publicado em 01/05/2014 ENG
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The gastrointestinal tract is equipped with a highly specialized intrinsic immune system. However, the intestine is exposed to a high antigenic burden that requires a fast, nonspecific response -so-called innate immunity- to maintain homeostasis and protect the body from incoming pathogens. In the last decade multiple studies helped to unravel the particular developmental requirements and specific functions of the cells that play a role in innate immunity. In this review we shall focus on innate lymphoid cells, a newly discovered, heterogeneous set of cells that derive from an Id2-dependent lymphoid progenitor cell population. These cells have been categorized on the basis of the pattern of cytokines that they secrete, and the transcription factors that regulate their development and functions. Innate lymphoid cells play a role in the early response to pathogens, the anatomical contention of the commensal flora, and the maintenance of epithelial integrity. Amongst the various innate lymphoid cells we shall lay emphasis on a subpopulation with several peculiarities, namely that of natural killer T cells, a subset of T lymphocytes that express both T-cell and NK-cell receptors. The most numerous fraction of the NKT population are the so-called invariant NKT or iNKT cells. These iNKT cells have an invariant TCR and recognize the glycolipidic structures presented by the CD1d molecule...