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Innate immunity to Paracoccidioides brasiliensis infection

CALICH, Vera Lucia Garcia; COSTA, Tania Alves da; FELONATO, Maira; ARRUDA, Celina; BERNARDINO, Simone; LOURES, Flavio Vieira; RIBEIRO, Laura Raquel Rios; VALENTE-FERREIRA, Rita de Cassia; PINA, Adriana
Fonte: SPRINGER Publicador: SPRINGER
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
66.5%
Innate immunity is based in pre-existing elements of the immune system that directly interact with all types of microbes leading to their destruction or growth inhibition. Several elements of this early defense mechanism act in concert to control initial pathogen growth and have profound effect on the adaptative immune response that further develops. Although most studies in paracoccidioidomycosis have been dedicated to understand cellular and humoral immune responses, innate immunity remains poorly defined. Hence, the main purpose of this review is to present and discuss some mechanisms of innate immunity developed by resistant and susceptible mice to Paracoccidioides brasiliensis infection, trying to understand how this initial host-pathogen interface interferes with the protective or deleterious adaptative immune response that will dictate disease outcome. An analysis of some mechanisms and mediators of innate immunity such as the activation of complement proteins, the microbicidal activity of natural killer cells and phagocytes, the production of inflammatory eicosanoids, cytokines, and chemokines among others, is presented trying to show the important role played by innate immunity in the host response to P. brasiliensis infection.

O receptor de reconhecimento de patógenos TLR-2 e a proteína adaptadora MYD88 apresentam um importante papel na infecção murina contra o Paracoccidioides brasiliensis; The pathogen recognition receptor TLR-2 and the adaptor protein MyD88 have an important role in the innate and adaptive immunity against Paracoccidioides brasiliensis infection

Loures, Flávio Vieira
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 08/03/2010 PT
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56.45%
Os mecanismos imunológicos que governam a interação entre o fungo Paracoccidioides brasiliensis e o hospedeiro têm sido pouco estudados. Tanto os componentes do fungo como os receptores dos fagócitos envolvidos nesta interação são pouco conhecidos. Baseados nestes fatos, nosso trabalho teve por objetivo caracterizar in vitro e in vivo o envolvimento do receptor Toll Like-2 (TLR-2) e da proteína adaptadora MyD88 (myeloid differentiation primary response gene 88) na infecção de camundongos pelo P. brasiliensis. O TLR-2 é um receptor da imunidade inata envolvido no reconhecimento de PAMPs (padrões moleculares associados aos patógenos), enquanto que MyD88 é uma molécula envolvida na sinalização celular induzida por muitos TLRs e que culmina com a ativação de vários fatores de transcrição, entre eles o NFB, envolvidos na ativação de genes ligados à resposta inflamatória. Para tanto, utilizamos camundongos C57Bl/6 deficientes e normais para TLR-2 e para MyD88. Demonstramos que, comparado ao grupo controle, animais TLR2-/- apresentavam uma infecção pulmonar menos grave associada com menor síntese de óxido nítrico (NO). Resultados equivalentes foram obtidos com macrófagos peritoneais e alveolares infectados in vitro. Inesperadamente...

Imunidade inata na asma fatal; Innate immunity in fatal asthma

Ferreira, Diogenes Seraphim
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 13/08/2010 PT
Relevância na Pesquisa
66.34%
INTRODUÇÃO: A inflamação das vias aéreas na asma envolve respostas imunes inatas. Os receptores do tipo Toll (Toll-like receptors, TLRs) e a citocina linfopoetina do estroma tímico (thymic stromal lymphopoietin, TSLP) estão envolvidos na inflamação brônquica da asma, mas a expressão destas proteínas em vias aéreas grandes e pequenas de asmáticos ainda não foi investigada. Os objetivos deste estudo foram analisar a expressão protéica de TLR2, TLR3, TLR4 e TSLP em vias aéreas grandes e pequenas de asmáticos, comparar sua expressão entre asmáticos tabagistas e não tabagistas e investigar se a expressão dos TLRs está associada à infecção por Chlamydophila pneumoniae e Mycoplasma pneumoniae. MÉTODOS: Foram analisadas por método imuno-histoquímico e análise de imagens as expressões de TLR2, TLR3, TLR4 e TSLP em vias aéreas grandes e pequenas de 24 indivíduos falecidos por asma (13 não tabagistas e 11 tabagistas) e 9 controles não asmáticos. A análise das proteínas foi realizada em quatro regiões das vias aéreas: camadas epitelial, interna, muscular e externa. A presença de C. pneumoniae e M. pneumoniae no tecido pulmonar foi investigada por meio de reação em cadeia da polimerase em tempo real. RESULTADOS: Os indivíduos asmáticos apresentaram maior expressão de TLR2 nas camadas epitelial e externa de vias aéreas grandes e pequenas...

Innate immunity and regulatory T-cells in human Chagas disease: what must be understood?

Sathler-Avelar,Renato; Vitelli-Avelar,Danielle Marquete; Teixeira-Carvalho,Andréa; Martins-Filho,Olindo Assis
Fonte: Instituto Oswaldo Cruz, Ministério da Saúde Publicador: Instituto Oswaldo Cruz, Ministério da Saúde
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/07/2009 EN
Relevância na Pesquisa
66.48%
There is a general consensus that during chronic Trypanosoma cruzi infection, the host immune system induces complex processes to ensure the control of parasite growth while preserving the potential to mount and maintain a life-long controlled humoral and cellular immune response against the invading pathogen. This review summarises evidence in an attempt to elucidate "what must be understood" to further clarify the role of innate immunity in the development/maintenance of clinical Chagas disease and the impact of etiological treatment on host immunity, highlighting the contributions of the innate immunity and regulatory T (Treg) cells. Recently, increasing focus on innate immunity suggest that chronic T. cruzi infection may cause morbidity when innate effector functions, or the down-regulation of adaptive regulatory mechanisms are lacking. In this context, stable asymptomatic host-parasite interactions seem to be influenced by the effector/regulatory balance with the participation of macrophages, natural killer (NK) and CD8+ T cells in parallel with the establishment of regulatory mechanisms mediated by NKT and Treg cells. Moreover, a balanced innate immune activation state, apart from Treg cells, may play a role in controlling the adverse events triggered by the massive antigen release induced by trypanosomicidal agents during Chagas disease etiological treatment.

Ozone and Pulmonary Innate Immunity

Hollingsworth, John W.; Kleeberger, Steven R.; Foster, W. Michael
Fonte: American Thoracic Society Publicador: American Thoracic Society
Tipo: Artigo de Revista Científica
Publicado em /07/2007 EN
Relevância na Pesquisa
66.41%
Ambient ozone (O3) is a commonly encountered environmental air pollutant with considerable impact on public health. Many other inhaled environmental toxicants can substantially affect pulmonary immune responses. Therefore, it is of considerable interest to better understand the complex interaction between environmental airway irritants and immunologically based human disease. The innate immune system represents the first line of defense against microbial pathogens. Intact innate immunity requires maintenance of an intact barrier to interface with the external environment, effective phagocytosis of microbial pathogens, and precise detection of pathogen-associated molecular patterns. We use ambient O3 as a model to highlight the importance of understanding the role of exposure to ubiquitous air toxins and regulation of basic immune function. Inhalation of O3 is associated with impaired antibacterial host defense, in part related to disruption of epithelial barrier and effective phagocytosis of pathogens. The functional response to ambient O3 seems to be dependent on many components of the innate immune signaling. In this article, we review the complex interaction between inhalation of O3 and pulmonary innate immunity.

Comparative Genomics RNAi Screen Identifies Eftud2 as a Novel Regulator of Innate Immunity

De Arras, Lesly; Laws, Rebecca; Leach, Sonia M.; Pontis, Kyle; Freedman, Jonathan H.; Schwartz, David A.; Alper, Scott
Fonte: Genetics Society of America Publicador: Genetics Society of America
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
56.53%
The extent of the innate immune response is regulated by many positively and negatively acting signaling proteins. This allows for proper activation of innate immunity to fight infection while ensuring that the response is limited to prevent unwanted complications. Thus mutations in innate immune regulators can lead to immune dysfunction or to inflammatory diseases such as arthritis or atherosclerosis. To identify novel innate immune regulators that could affect infectious or inflammatory disease, we have taken a comparative genomics RNAi screening approach in which we inhibit orthologous genes in the nematode Caenorhabditis elegans and murine macrophages, expecting that genes with evolutionarily conserved function also will regulate innate immunity in humans. Here we report the results of an RNAi screen of approximately half of the C. elegans genome, which led to the identification of many candidate genes that regulate innate immunity in C. elegans and mouse macrophages. One of these novel conserved regulators of innate immunity is the mRNA splicing regulator Eftud2, which we show controls the alternate splicing of the MyD88 innate immunity signaling adaptor to modulate the extent of the innate immune response.

Requirement for interleukin-1 to drive brain inflammation reveals tissue-specific mechanisms of innate immunity

Giles, James A; Greenhalgh, Andrew D; Davies, Claire L; Denes, Adam; Shaw, Tovah; Coutts, Graham; Rothwell, Nancy J; McColl, Barry W; Allan, Stuart M
Fonte: BlackWell Publishing Ltd Publicador: BlackWell Publishing Ltd
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
66.36%
The immune system is implicated in a wide range of disorders affecting the brain and is, therefore, an attractive target for therapy. Interleukin-1 (IL-1) is a potent regulator of the innate immune system important for host defense but is also associated with injury and disease in the brain. Here, we show that IL-1 is a key mediator driving an innate immune response to inflammatory challenge in the mouse brain but is dispensable in extracerebral tissues including the lung and peritoneum. We also demonstrate that IL-1α is an important ligand contributing to the CNS dependence on IL-1 and that IL-1 derived from the CNS compartment (most likely microglia) is the major source driving this effect. These data reveal previously unknown tissue-specific requirements for IL-1 in driving innate immunity and suggest that IL-1-mediated inflammation in the brain could be selectively targeted without compromising systemic innate immune responses that are important for resistance to infection. This property could be exploited to mitigate injury- and disease-associated inflammation in the brain without increasing susceptibility to systemic infection, an important complication in several neurological disorders.

Innate Immunity and Resistance to Tolerogenesis in Allotransplantation

Benichou, Gilles A.; Tonsho, Makoto; Tocco, Georges; Nadazdin, Ognjenka M.; Madsen, Joren Christian
Fonte: Frontiers Research Foundation Publicador: Frontiers Research Foundation
Tipo: Artigo de Revista Científica
EN_US
Relevância na Pesquisa
66.38%
The development of immunosuppressive drugs to control adaptive immune responses has led to the success of transplantation as a therapy for end-stage organ failure. However, these agents are largely ineffective in suppressing components of the innate immune system. This distinction has gained in clinical significance as mounting evidence now indicates that innate immune responses play important roles in the acute and chronic rejection of whole organ allografts. For instance, whereas clinical interest in natural killer (NK) cells was once largely confined to the field of bone marrow transplantation, recent findings suggest that these cells can also participate in the acute rejection of cardiac allografts and prevent tolerance induction. Stimulation of Toll-like receptors (TLRs), another important component of innate immunity, by endogenous ligands released in response to ischemia/reperfusion is now known to cause an inflammatory milieu favorable to graft rejection and abrogation of tolerance. Emerging data suggest that activation of complement is linked to acute rejection and interferes with tolerance. In summary, the conventional wisdom that the innate immune system is of little importance in whole organ transplantation is no longer tenable. The addition of strategies that target TLRs...

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
Relevância na Pesquisa
66.44%
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)...

Innate Immunity and the Evolution of Resistance to an Emerging Infectious Disease in a Wild Bird

Bonneaud, Camille; Balenger, Susan L.; Zhang, Jiangwen; Edwards, Scott V.; Hill, Geoffrey E.
Fonte: Wiley Blackwell (Blackwell Publishing) Publicador: Wiley Blackwell (Blackwell Publishing)
Tipo: Artigo de Revista Científica
EN_US
Relevância na Pesquisa
56.4%
Innate immunity is expected to play a primary role in conferring resistance to novel infectious diseases, but few studies have attempted to examine its role in the evolution of resistance to emerging pathogens in wild vertebrate populations. Here, we used experimental infections and cDNA microarrays to examine whether changes in the innate and/or acquired immune responses likely accompanied the emergence of resistance in house finches (Carpodacus mexicanus) in the eastern United States subject to a recent outbreak of conjunctivitis-causing bacterium (Mycoplasma gallisepticum—MG). Three days following experimental infection with MG, we observed differences in the splenic transcriptional responses between house finches from eastern U.S. populations, with a 12-year history of MG exposure, versus western U.S. populations, with no history of exposure to MG. In particular, western birds down-regulated gene expression, while eastern finches showed no expression change relative to controls. Studies involving poultry have shown that MG can manipulate host immunity, and our observations suggest that pathogen manipulation occurred only in finches from the western populations, outside the range of MG. Fourteen days after infection, eastern finches...

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
Relevância na Pesquisa
56.52%
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...

Innate immunity in the paranasal sinuses: a review of nasal host defenses

Ooi, E.; Wormald, P.J.; Tan, L.W.
Fonte: Ocean Side Publications Inc Publicador: Ocean Side Publications Inc
Tipo: Artigo de Revista Científica
Publicado em //2008 EN
Relevância na Pesquisa
66.41%
BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disorder of the paranasal sinuses. An abnormal host response to common bacterial or fungal pathogens is thought to be an important factor in the disease process. Host sinonasal epithelium plays an important role in initially recognizing the presence of microbes and responding by increasing production of antimicrobial peptides and cytokines, with recruitment of phagocytes and lymphocytes of the adaptive immune system, to eliminate the infection. Recently, the innate immune system and its complex interplay with the adaptive immune system are increasingly being recognized as important in the pathogenesis of chronic inflammatory diseases such as asthma and CRS. METHODS: Review of recent findings on innate immunity in the pathogenesis of CRS. RESULTS: New areas of research into potentially novel therapies for CRS are highlighted in this review, with emphasis on toll-like receptors, antimicrobial peptides (cathelicidins and defensins), and surfactant proteins. CONCLUSION: This review provides an overview of innate immunity in the sinonasal tract and discusses potential use of innate immune peptides as treatments against fungi, biofilms, and superantigens in CRS.; Ooi, Eng Hooi; Wormald...

Innate Immunity

Ooi, E.; Psaltis, A.; Witterick, I.; Wormald, P.J.
Fonte: W B Saunders Co Publicador: W B Saunders Co
Tipo: Artigo de Revista Científica
Publicado em //2010 EN
Relevância na Pesquisa
66.35%
Innate immunity is an exciting area of research in rhinology because emerging evidence suggests that abnormal local immune responses, rather than pathogen-specific adaptive immunity, may play a more important role in the pathogenesis of chronic rhinosinusitis (CRS). This article reviews important recent research regarding the innate immune system and CRS, with particular focus on the role of pattern recognition receptors, antimicrobial peptides and biofilms, epithelial ciliary function, cystic fibrosis, and cigarette smoking, and on areas for future research and therapy.; http://www.elsevier.com/wps/find/journaldescription.cws_home/623170/description#description; Eng H. Ooi, Alkis J. Psaltis, Ian J. Witterick and Peter-John Wormald

Drosophila 14-3-3ε has a crucial role in anti-microbial peptide secretion and innate immunity; Drosophila 14-3-3epsilon has a crucial role in anti-microbial peptide secretion and innate immunity

Shandala, T.; Woodcock, J.; Ng, Y.; Biggs, L.; Skoulakis, E.; Brooks, D.; Lopez, A.
Fonte: Company of Biologists Ltd Publicador: Company of Biologists Ltd
Tipo: Artigo de Revista Científica
Publicado em //2011 EN
Relevância na Pesquisa
66.44%
The secretion of anti-microbial peptides is recognised as an essential step in innate immunity, but there is limited knowledge of the molecular mechanism controlling the release of these effectors from immune response cells. Here, we report that Drosophila 14-3-3 mutants exhibit reduced survival when infected with either Gram-positive or Gram-negative bacteria, indicating a functional role for 14-3-3 in innate immunity. In 14-3-3 mutants, there was a reduced release of the anti-microbial peptide Drosomycin into the haemolymph, which correlated with an accumulation of Drosomycin-containing vesicles near the plasma membrane of cells isolated from immune response tissues. Drosomycin appeared to be delivered towards the plasma membrane in Rab4- and Rab11-positive vesicles and smaller Rab11-positive vesicles. RNAi silencing of Rab11 and Rab4 significantly blocked the anterograde delivery of Drosomycin from the perinuclear region to the plasma membrane. However, in 14-3-3 mutants there was an accumulation of small Rab11-positive vesicles near the plasma membrane. This vesicular phenotype was similar to that observed in response to the depletion of the vesicular Syntaxin protein Syx1a. In wild-type Drosophila immune tissue, 14-3-3 was detected adjacent to Rab11...

Characterisation of the Role of LysM Receptor-Like Kinases and the CHIA Chitinase in the Perception of Peptidoglycan and in the Innate Immunity of Arabidopsis thaliana; Charakterisierung der Rolle der LysM Rezeptor-ähnlichen Kinasen und der CHIA Chitinase in der Perzeption von Peptidoglycan und der angeborenen Immunität von Arabidopsis thaliana

Grabherr, Heini Marjatta
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
EN
Relevância na Pesquisa
66.42%
Plants as sessile organisms cannot escape, when they are confronted with harmful pathogens. Instead, they are weaponed with sophisticated and highly complex molecular responses that allow them to defend themselves. The innate immunity forms the basis for the self-defense of higher organisms, including mammals, invertebrates and plants. During the basal immune response, conserved microbial signatures are perceived by pattern recognition receptors and trigger a variety of defense reactions leading to protection of the plant tissue and resistance. The bacterial cell wall component peptidoglycan (PGN) is one of such conserved signatures activating the plant defense responses, however the molecular mechanisms of its recognition was until now not understood. The importance of LysM-domain containing plant proteins in the recognition of carbohydrate ligands, such as chitin and lipochitooligosaccharides, has been elucidated in the last years. Due to the structural similarities between chitin, lipochitooligosaccharide and peptidoglycan, members of this protein family provide interesting candidates for a putative PGN receptor. The reverse genetics approach performed in this work revealed a LysM receptor kinase, CERK1, to be involved in PGN perception. CERK1 is not only essential for the PGN-mediated activation of defense responses in Arabidopsis thaliana...

Gene Expression Studies on the Evolution of Development and Innate Immunity in the Nematode Pristionchus pacificus; Genexpressions-Studien zur Evolution der Entwicklung und Angeborenen Immunität des Nematoden Pristionchus pacificus

Sinha, Amit
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
EN
Relevância na Pesquisa
66.25%
Evolutionary biology aims to explain the enormous biological diversity by employing diverse approaches including systematics, ecology, population genetics and developmental biology. Comparison of a set of traits across different species is a very fruitful approach in evolutionary biology. With this goal in mind, the nematode Pristionchus pacificus has been developed as a model system for comparative analysis vis-a-vis the extensively studied nematode model Caenorhabditis elegans, and serves to integrate insights from developmental biology, ecology and population genetics. Comparison of processes such as vulva development, sex-determination pathways, gonad development and developmental polyphenisms such as dauer development and mouth-form dimorphism has revealed that highly conserved genetic pathways can be used in different configurations to generate macroevolutionary changes. The sequencing of the whole genome of P. pacificus opened a new avenue for comparative genomics, e.g. it has a larger genome and a higher gene content than C. elegans. Many factors contribute to this increase in gene number, including expansion of certain gene families, horizontal gene transfer, and origin of lineage specific pioneer' genes, many of which might have a potential role in its ecological adaptations related to beetle association. However...

Interacciones de Brucella abortus con la inmunidad innata del sistema nervioso central como determinante de patogénesis de la neurobrucelosis; Interactions of Brucella abortus with innate immunity of central nervous system as a determinant of neurobrucellosis

García Samartino, Clara
Fonte: Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires Publicador: Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires
Tipo: info:eu-repo/semantics/doctoralThesis; tesis doctoral; info:eu-repo/semantics/publishedVersion Formato: application/pdf
Publicado em //2010 SPA
Relevância na Pesquisa
66.25%
La invasión al sistema nervioso central (SNC) por bacterias del genero Brucella resulta en un desorden inflamatorio llamado neurobrucelosis. En este trabajo nosotros presentamos evidencia in vivo e in vitro mostrando que B. abortus y sus lipoproteínas activan la inmunidad innata del SNC, originando una respuesta inflamatoria que lleva a la astrogliosis, una característica típica de neurobrucelosis. Inyecciones intracraneales de B. abortus muerta por calor (HKBA) o de la proteína de la membrana externa 19 (Omp19), una lipoproteína de B. abortus utilizada como modelo, indujeron astrogliosis concomitantemente con un infiltrado neutrofilico en el cuerpo estriado de los ratones. La infección de astrocitos y microglia con B. abortus incitó la secreción de IL-6, IL-1beta, TNF-alfa, MCP-1 y KC (CXCL1). HKBA también estimuló la liberación de estos mediadores inflamatorios, sugiriendo la independencia de la viabilidad bacteriana en este fenómeno e implicando a un componente estructural de la bacteria. De acuerdo con esto, Omp19 indujo el mismo patrón de secreción de citoquinas y quimiocinas. La respuesta inflamatoria desencadenada por Omp19 estuvo mediada por TLR2, ya que cultivos de células gliales provenientes de ratones TLR2 KO no promovieron la secreción de mediadores proinflamatorios. Sin embargo este receptor no media la infección ni la replicación de la bacteria en astrocitos o en microglía. La infección con B. abortus promovio apoptosis de astrocitos pero no de microglia. HKBA y Omp19 indujeron...

Salmonella Suppress Innate Immunity by Targeting Mast Cells

Choi, Hae Woong
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Dissertação
Publicado em //2014
Relevância na Pesquisa
66.41%

Mast cells (MCs) are increasingly recognized as powerful sentinel cells responsible for modulating the early immune responses to a wide range of infectious agents. This protective role is attributable in part to their preponderance at the host-environment interface and their innate capacity to rapidly release modulators of immune cell trafficking which promotes the early recruitment of pathogen-clearing immune cells from the blood. However, host-adapted pathogens had been a critical threat to human for a long time because they have evolved mechanisms directed at overcoming protective immunity.

In this work, we outline Salmonella enterica serovar Typhimurium has evolved a novel mechanism to inactivate peripheral MCs resulting in limited neutrophil responses at infection sites in early stage of infection. Because of the delay in bacterial clearance at the point of entry, Salmonella are able to multiply and rapidly disseminate to distal sites. Suppression of local MCs' degranulation restricted outflow of vascular contents into infection sites, thus facilitating bacterial spread.

We discover MC suppression is mediated by the Salmonella Protein Tyrosine Phosphatase (SptP), which shares structural homology with Yersinia YopH. Interestingly...

Using Genetic Analysis and the Model Organism Caenorhabditis Elegans to Identify Bacterial Virulence Factors and Innate Immune Defenses against Pathogens

Styer, Katie Letitia
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Dissertação Formato: 3211715 bytes; application/pdf
Publicado em 25/04/2008 EN_US
Relevância na Pesquisa
56.46%

An estimated twenty-five percent of the fifty-seven million annual deaths worldwide can be directly attributed to infectious disease. Mammals contain both adaptive and innate immune systems to deal with invading pathogens. The genetic model organism Caenorhabditis elegans lacks an adaptive immune system, which makes it a powerful model organism to study the innate immune system without the added complexity of an adaptive immune system. Multiple human pathogens can cause lethal infections in C. elegans and several C. elegans innate immune pathways have been identified that are conserved with mammals and protect the nematode from infection. The goal of this work was to identify novel bacterial virulence factors and innate immune defenses against pathogens by using the genetic model organism C. elegans. We established C. elegans as a model for Yersinia pestis infection and used this model to identify novel bacterial virulence factors that were also important for virulence in a mammalian model of infection. Previous studies demonstrated that C. elegans can identify bacterial pathogens using sensory neurons and activate an avoidance response that requires components of G-protein signaling pathways. We screened forty C. elegans strains containing mutations in chemosensory G-protein coupled receptors for altered survival on pathogen and identified npr-1 to be required for full C. elegans defense against pathogens. We found that activation of the NPR-1 nervous circuit enhances host susceptibility to microbial infection while inhibition of the circuit boosts innate immunity. This data provides the first evidence that innate immunity in C. elegans is directly linked to the nervous system and establishes the nematode as a novel system to study neuroimmunology. From this work...

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
Relevância na Pesquisa
56.39%
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...