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1.
Nat Commun ; 10(1): 2292, 2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31123263

RESUMO

The wheat Pm3 resistance gene against the powdery mildew pathogen occurs as an allelic series encoding functionally different immune receptors which induce resistance upon recognition of isolate-specific avirulence (AVR) effectors from the pathogen. Here, we describe the identification of five effector proteins from the mildew pathogens of wheat, rye, and the wild grass Dactylis glomerata, specifically recognized by the PM3B, PM3C and PM3D receptors. Together with the earlier identified AVRPM3A2/F2, the recognized AVRs of PM3B/C, (AVRPM3B2/C2), and PM3D (AVRPM3D3) belong to a large group of proteins with low sequence homology but predicted structural similarities. AvrPm3b2/c2 and AvrPm3d3 are conserved in all tested isolates of wheat and rye mildew, and non-host infection assays demonstrate that Pm3b, Pm3c, and Pm3d are also restricting the growth of rye mildew on wheat. Furthermore, divergent AVR homologues from non-adapted rye and Dactylis mildews are recognized by PM3B, PM3C, or PM3D, demonstrating their involvement in host specificity.


Assuntos
Ascomicetos/fisiologia , Proteínas Fúngicas/imunologia , Especificidade de Hospedeiro , Doenças das Plantas/imunologia , Proteínas de Plantas/imunologia , Triticum/imunologia , Ascomicetos/isolamento & purificação , Ascomicetos/patogenicidade , Dactylis/microbiologia , Resistência à Doença/imunologia , Grão Comestível/imunologia , Grão Comestível/microbiologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Genoma Fúngico , Estudo de Associação Genômica Ampla , Proteínas NLR/imunologia , Proteínas NLR/metabolismo , Doenças das Plantas/microbiologia , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Secale/microbiologia , Tabaco/genética , Tabaco/microbiologia , Triticum/microbiologia
2.
Int J Mol Sci ; 20(8)2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30995767

RESUMO

To ward off pathogens and pests, plants use a sophisticated immune system. They use pattern-recognition receptors (PRRs), as well as nucleotide-binding and leucine-rich repeat (NB-LRR) domains, for detecting nonindigenous molecular signatures from pathogens. Plant PRRs induce local and systemic immunity. Plasma-membrane-localized PRRs are the main components of multiprotein complexes having additional transmembrane and cytosolic kinases. Topical research involving proteins and their interactive partners, along with transcriptional and posttranscriptional regulation, has extended our understanding of R-gene-mediated plant immunity. The unique LRR domain conformation helps in the best utilization of a surface area and essentially mediates protein-protein interactions. Genome-wide analyses of inter- and intraspecies PRRs and NB-LRRs offer innovative information about their working and evolution. We reviewed plant immune responses with relevance to PRRs and NB-LRRs. This article focuses on the significant functional diversity, pathogen-recognition mechanisms, and subcellular compartmentalization of plant PRRs and NB-LRRs. We highlight the potential biotechnological application of PRRs and NB-LRRs to enhance broad-spectrum disease resistance in crops.


Assuntos
Proteínas NLR/imunologia , Doenças das Plantas/imunologia , Imunidade Vegetal , Proteínas de Plantas/imunologia , Plantas/imunologia , Receptores de Reconhecimento de Padrão/imunologia , Produtos Agrícolas/imunologia , Imunidade Inata
3.
PLoS Biol ; 16(12): e2005821, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30540748

RESUMO

The ability to induce a defense response after pathogen attack is a critical feature of the immune system of any organism. Nucleotide-binding leucine-rich repeat receptors (NLRs) are key players in this process and perceive the occurrence of nonself-activities or foreign molecules. In plants, coevolution with a variety of pests and pathogens has resulted in repertoires of several hundred diverse NLRs in single individuals and many more in populations as a whole. However, the mechanism by which defense signaling is triggered by these NLRs in plants is poorly understood. Here, we show that upon pathogen perception, NLRs use their N-terminal domains to transactivate other receptors. Their N-terminal domains homo- and heterodimerize, suggesting that plant NLRs oligomerize upon activation, similar to the vertebrate NLRs; however, consistent with their large number in plants, the complexes are highly heterometric. Also, in contrast to metazoan NLRs, the N-terminus, rather than their centrally located nucleotide-binding (NB) domain, can mediate initial partner selection. The highly redundant network of NLR interactions in plants is proposed to provide resilience to perturbation by pathogens.


Assuntos
Proteínas NLR/genética , Proteínas NLR/imunologia , Proteínas de Plantas/genética , Genoma de Planta/genética , Genoma de Planta/imunologia , Imunidade Inata , Alface/genética , Doenças das Plantas/imunologia , Imunidade Vegetal/genética , Imunidade Vegetal/imunologia , Plantas/genética , Plantas/imunologia , Domínios Proteicos/genética , Análise de Sequência de Proteína , Transdução de Sinais
4.
Clin Exp Rheumatol ; 36 Suppl 110(1): 3-9, 2018 Jan-Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29742053

RESUMO

An apparently unprovoked recurrent inflammation is the quintessential hallmark of autoinflammatory diseases (AIDs), a large and heterogeneous group of disorders in which there is poor regulation of the innate immune system with no clearly demonstrated autoimmune machinery involvement. Innate immunity pathways are diverse and our understanding of their molecular composition and function is continuously expanding. The impaired immune responses we observe in monogenic AIDs, mostly in the hereditary periodic fever syndromes, is officiated by target molecules of microbial origin (pathogen-associated molecular patterns) and also host molecules (danger-associated molecular patterns). Further crucial components of innate immune mechanisms that contribute differently in the deregulated inflammatory patterns of different AIDs include Toll-like receptors, Nod-like receptors, scaffolding proteins (such as the caspase recruitment domain of proteins), cytosolic DNA-sensing molecules, inflammatory multi-protein complexes (referred to as inflammasomes), complement system, and others. In recent years, the knowledge of protean molecular pathways responsible for the most common monogenic AIDs has expanded, in parallel with very recent extraordinary technological advances, allowing the identification and characterisation of some unknown aspects of the innate immunity. This review will list and describe the most common monogenic febrile syndromes belonging to AIDs and will focus on current insights dealing with their pathologic processes.


Assuntos
Domínio de Ativação e Recrutamento de Caspases/imunologia , Proteínas do Sistema Complemento/imunologia , Doenças Hereditárias Autoinflamatórias/imunologia , Imunidade Inata/imunologia , Inflamassomos/imunologia , Inflamação/imunologia , Proteínas NLR/imunologia , Receptores Toll-Like/imunologia , Doenças Hereditárias Autoinflamatórias/genética , Humanos , Transdução de Sinais
5.
Plant Sci ; 269: 85-93, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29606220

RESUMO

In due course of evolution many pathogens alter their effector molecules to modulate the host plants' metabolism and immune responses triggered upon proper recognition by the intracellular nucleotide-binding oligomerization domain containing leucine-rich repeat (NLR) proteins. Likewise, host plants have also evolved with diversified NLR proteins as a survival strategy to win the battle against pathogen invasion. NLR protein indeed detects pathogen derived effector proteins leading to the activation of defense responses associated with programmed cell death (PCD). In this interactive process, genome structure and plasticity play pivotal role in the development of innate immunity. Despite being quite conserved with similar biological functions in all eukaryotes, the intracellular NLR immune receptor proteins happen to be structurally distinct. Recent studies have made progress in identifying transcriptional regulatory complexes activated by NLR proteins. In this review, we attempt to decipher the intracellular NLR proteins mediated surveillance across the evolutionarily diverse taxa, highlighting some of the recent updates on NLR protein compartmentalization, molecular interactions before and after activation along with insights into the finer role of these receptor proteins to combat invading pathogens upon their recognition. Latest information on NLR sensors, helpers and NLR proteins with integrated domains in the context of plant pathogen interactions are also discussed.


Assuntos
Interações Hospedeiro-Patógeno/genética , Proteínas NLR/imunologia , Imunidade Vegetal , Plantas/imunologia , Interações Hospedeiro-Patógeno/imunologia , Proteínas NLR/genética , Plantas/genética
6.
Inflamm Res ; 67(6): 479-493, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29353310

RESUMO

INTRODUCTION: Molecular mechanisms underlying the interactions between Pseudomonas aeruginosa, the common opportunistic pathogen in cystic fibrosis individuals, and host induce a number of marked inflammatory responses and associate with complex therapeutic problems due to bacterial resistance to antibiotics in chronic stage of infection. METHODS: Pseudomonas aeruginosa is recognized by number of pattern recognition receptors (PRRs); NOD-like receptors (NLRs) are a class of PRRs, which can recognize a variety of endogenous and exogenous ligands, thereby playing a critical role in innate immunity. RESULTS: NLR activation initiates forming of a multi-protein complex called inflammasome that induces activation of caspase-1 and resulted in cleavage of pro-inflammatory cytokines interleukin (IL)-1ß and IL-18. When the IL-1ß is secreted excessively, this causes tissue damage and extensive inflammatory responses that are potentially hazardous for the host. CONCLUSIONS: Recent evidence has laid out inflammasome-forming NLR far beyond inflammation. This review summarizes current knowledge regarding the various roles played by different NLRs and associated down-signals, either in recognition of P. aeruginosa or may be associated with such bacterial pathogen infection, which may relate to for the complexity of lung diseases caused by P. aeruginosa.


Assuntos
Interações Hospedeiro-Patógeno/imunologia , Proteínas NLR/imunologia , Infecções por Pseudomonas/imunologia , Animais , Fibrose Cística/imunologia , Humanos , Pseudomonas aeruginosa/fisiologia , Transdução de Sinais
7.
Arch Virol ; 163(3): 639-647, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29198037

RESUMO

Avian leukosis virus J (ALVJ) infection induces hematopoietic malignancy in myeloid leukemia and hemangioma in chickens. However, little is known about the mechanisms underpinning the unique pathogenesis of ALVJ. In this study, we investigated the gene expression profiles of ALVJ-infected chicken cells and performed a comprehensive analysis of the long non-coding RNAs (lncRNAs) in CEF cells using RNA-Seq. As a result, 36 differentially expressed lncRNAs and 91 genes (FC > 2 and q-values < 0.05) were identified. Bioinformatics analysis revealed that these differentially expressed genes are involved in the innate immune response. Target prediction analysis revealed that these lncRNAs may act in cis or trans and affect the expression of genes which are involved in the anti-viral innate immune responses. Toll-like receptor, RIG-I receptor, NOD-like receptor and JAK-STAT signaling pathways were enriched. Notably, the induced expression of innate immunity genes, including B2M, DHX58, IFI27L2, IFIH1, IRF10, ISG12(2), MX, OAS*A, RSAD2, STAT1, TLR3, IL4I1, and IRF1 (FC > 2 and correlation > 0.95), were highly correlated with the upregulation of several lncRNAs, including MG066618, MG066617, MG066601, MG066629, MG066609 and MG066616. These findings identify the expression profile of lncRNAs in chicken CEF cells infected by ALVJ virus and provide new insights into the molecular mechanisms of ALVJ infection.


Assuntos
Vírus da Leucose Aviária/genética , Fibroblastos/virologia , Interações Hospedeiro-Patógeno , RNA Longo não Codificante/genética , Transcriptoma/imunologia , Animais , Vírus da Leucose Aviária/crescimento & desenvolvimento , Vírus da Leucose Aviária/imunologia , Linhagem Celular , Embrião de Galinha , Biologia Computacional , Proteína DEAD-box 58/genética , Proteína DEAD-box 58/imunologia , Fibroblastos/imunologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Imunidade Inata , Janus Quinase 1/genética , Janus Quinase 1/imunologia , Proteínas NLR/genética , Proteínas NLR/imunologia , RNA Longo não Codificante/imunologia , Fatores de Transcrição STAT/genética , Fatores de Transcrição STAT/imunologia , Análise de Sequência de RNA , Transdução de Sinais , Receptores Toll-Like/genética , Receptores Toll-Like/imunologia
8.
Curr Issues Mol Biol ; 25: 43-60, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28875939

RESUMO

Following colonization of host tissues, bacterial pathogens encounter new niches in which they must gain access to nutrients and cope with stresses and defence signals generated by the host. For some pathogens, the adaptation to a new 'within-host' lifestyle involves modifications of envelope components that bear molecular patterns normally recognized by the host innate immune system. These new modified patterns limit host recognition, therefore promoting immune evasion and pathogenicity. In this review, we describe how envelope components like the peptidoglycan or lipopolysaccharide can be altered within the host to impair responses triggered by pattern recognition receptors (PRR). We also discuss the few cases reported to date of chemical modifications that occur in the envelope of some intracellular bacterial pathogens when they reside inside eukaryotic cells. These envelope alterations may have evolved due to the sentinel role performed by PRRs over pathogen-specific molecular patterns. The available data indicate that only selected pathogens seem to evade recognition due to 'within-host' envelope changes, with most of them displaying such patterns also in non host environments. Given the importance of these alterations, future studies should focus in the responsible pathogen regulators, most yet unknown, that could be targeted to prevent immune evasion.


Assuntos
Cápsulas Bacterianas/química , Lipopolissacarídeos/imunologia , Antígeno 96 de Linfócito/imunologia , Proteínas NLR/imunologia , Peptidoglicano/imunologia , Receptores Toll-Like/imunologia , Animais , Bactérias/crescimento & desenvolvimento , Bactérias/imunologia , Cápsulas Bacterianas/imunologia , Células Eucarióticas/imunologia , Células Eucarióticas/microbiologia , Regulação da Expressão Gênica , Humanos , Evasão da Resposta Imune , Imunidade Inata , Inflamassomos/imunologia , Inflamassomos/metabolismo , Lipopolissacarídeos/metabolismo , Antígeno 96 de Linfócito/genética , Proteínas NLR/genética , Peptidoglicano/metabolismo , Transdução de Sinais , Receptores Toll-Like/genética
9.
Curr Issues Mol Biol ; 25: 61-80, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28875940

RESUMO

Macrophages represent one of the first lines of host immune defenses against the invasion of pathogenic bacteria. Many receptors, immune signaling pathways and cellular processes in macrophages, including Toll-like receptors, Nod-like receptors, phagocytosis, autophagy and programmed cell death, are involved in combating the infection of bacterial pathogens. For efficient colonization in the host, bacterial pathogens have evolved diverse mechanisms to interfere with macrophage functions to evade host defenses. The major weapons utilized by bacterial pathogens are protein toxins and effectors secreted via specific bacterial secretion systems, including type I-VII secretion apparatuses. In recent years, great advances have been achieved in understanding how bacterial toxins and effectors subvert immune signaling and cellular processes of macrophages. In this review, we focus on the toxins and effectors that modulate the phagocytosis, intracellular immune signaling pathways, autophagy and programmed cell death processes of macrophages from the bacterium Legionella pneumophila, Shigella flexneri, Listeria monocytogenes, Salmonella spp., Yersinia spp., enteropathogenic E. coli and Mycobacterium tuberculosis.


Assuntos
Sistemas de Secreção Bacterianos/imunologia , Toxinas Bacterianas/biossíntese , Bactérias Gram-Negativas/imunologia , Bactérias Gram-Positivas/imunologia , Evasão da Resposta Imune , Macrófagos/imunologia , Animais , Apoptose , Autofagia , Sistemas de Secreção Bacterianos/genética , Toxinas Bacterianas/genética , Regulação da Expressão Gênica , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/crescimento & desenvolvimento , Humanos , Imunidade Inata , Macrófagos/microbiologia , Macrófagos/patologia , Proteínas NLR/genética , Proteínas NLR/imunologia , Fagocitose , Transdução de Sinais , Receptores Toll-Like/genética , Receptores Toll-Like/imunologia
10.
Curr Issues Mol Biol ; 25: 81-98, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28875941

RESUMO

Autophagy is a highly conserved catabolic process, degrading unnecessary or damaged components in the eukaryotic cell to maintain cellular homeostasis, but it is also an intrinsic cellular defence mechanism to remove invading pathogens. A crosstalk between autophagy and innate or adaptive immune responses has been recently reported, whereby autophagy influences both, innate and adaptive immunity like the production and secretion of pro-inflammatory cytokines or MHC class II antigen presentation to T cells. Pathogenic bacteria have evolved diverse strategies to manipulate autophagy, mechanisms that also impact host immune responses at different levels. Here we discuss the influence of autophagy on self-autonomous, innate and adaptive immunity and then focus on how bacterial mechanisms that shape autophagy may impact the host immune system.


Assuntos
Autofagia/genética , Bactérias Gram-Negativas/imunologia , Bactérias Gram-Positivas/imunologia , Interações Hospedeiro-Patógeno , Imunidade Inata , Linfócitos T/imunologia , Imunidade Adaptativa , Animais , Autofagossomos/imunologia , Autofagossomos/microbiologia , Citocinas/genética , Citocinas/imunologia , Regulação da Expressão Gênica , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/crescimento & desenvolvimento , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , Humanos , Proteínas NLR/genética , Proteínas NLR/imunologia , Transdução de Sinais , Linfócitos T/microbiologia , Receptores Toll-Like/genética , Receptores Toll-Like/imunologia
11.
Curr Issues Mol Biol ; 25: 133-168, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28875943

RESUMO

Human and animal pathogens are able to circumvent, at least temporarily, the sophisticated immune defenses of their hosts. Several serovars of the Gram-negative bacterium Salmonella enterica have been used as models for the study of pathogen-host interactions. In this review we discuss the strategies used by Salmonella to evade or manipulate three levels of host immune defenses: physical barriers, innate immunity and adaptive immunity. During its passage through the digestive system, Salmonella has to face the acidic pH of the stomach, bile and antimicrobial peptides in the intestine, as well as the competition with resident microbiota. After host cell invasion, Salmonella manipulates inflammatory pathways and the autophagy process. Finally, Salmonella evades the adaptive immune system by interacting with dendritic cells, and T and B lymphocytes. Mechanisms allowing the establishment of persistent infections are also discussed.


Assuntos
Linfócitos B/imunologia , Células Dendríticas/imunologia , Evasão da Resposta Imune , Imunidade Inata , Salmonella/imunologia , Linfócitos T/imunologia , Imunidade Adaptativa , Animais , Linfócitos B/microbiologia , Translocação Bacteriana , Células Dendríticas/microbiologia , Regulação da Expressão Gênica , Humanos , Intestinos/imunologia , Intestinos/microbiologia , Proteínas NLR/genética , Proteínas NLR/imunologia , Salmonella/crescimento & desenvolvimento , Transdução de Sinais , Estômago/imunologia , Estômago/microbiologia , Linfócitos T/microbiologia , Receptores Toll-Like/genética , Receptores Toll-Like/imunologia
12.
Curr Issues Mol Biol ; 25: 169-198, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28875944

RESUMO

Mycobacteria are intracellular pathogens that have macrophages as their main host cells. However, macrophages are also the primary line of defense against invading microorganisms. To survive in the intracellular compartment, virulent mycobacteria have developed several strategies to modulate the activation and the effector functions of macrophages. Despite this, antigen-specific T cells develop during infection. While T cell responses are critical for protection they can also contribute to the success of mycobacteria as human pathogens, as immunopathology associated with these responses facilitates transmission. Here, we provide a brief overview of different immune-evasion strategies of mycobacteria and their impact on the protective immune response. This understanding will further our knowledge in host-pathogen interactions and may provide critical insights for the development of novel host-specific therapies.


Assuntos
Células Dendríticas/imunologia , Evasão da Resposta Imune , Macrófagos/imunologia , Mycobacterium tuberculosis/imunologia , Mycobacterium/imunologia , Linfócitos T/imunologia , Imunidade Adaptativa , Animais , Citocinas/genética , Citocinas/imunologia , Células Dendríticas/microbiologia , Regulação da Expressão Gênica , Humanos , Imunidade Inata , Macrófagos/microbiologia , Mycobacterium/crescimento & desenvolvimento , Mycobacterium/patogenicidade , Mycobacterium tuberculosis/crescimento & desenvolvimento , Mycobacterium tuberculosis/patogenicidade , Proteínas NLR/genética , Proteínas NLR/imunologia , Fagossomos/imunologia , Transdução de Sinais , Linfócitos T/microbiologia , Receptores Toll-Like/genética , Receptores Toll-Like/imunologia
13.
Adv Exp Med Biol ; 1112: 255-280, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30637703

RESUMO

Recognition of a bacterial attack is the first and the most important step in clearing the bacteria from the body of the host. Towards this, the host innate immune system employs pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs), nucleotide-binding leucine-rich repeat-containing receptors (NLRs) and scavenger receptors (SRs) present mostly in innate immune cells. These receptors sense the presence of bacteria and help in spreading the signal to the host, which results in recruitment of other immune cells leading to the elimination of the bacteria from the system. Since their discovery, a lot has been established about these receptors. Their role has been elucidated not only in pathogen recognition but also in eradication of the dead cells from the system. This review is focussed mainly on their role in the bacterial recognition and how these receptors play a role in eliciting an immune response against bacteria in the host.


Assuntos
Bactérias/patogenicidade , Imunidade Inata , Receptores Imunológicos/imunologia , Humanos , Ligantes , Proteínas NLR/imunologia , Receptores de Reconhecimento de Padrão/imunologia , Receptores Depuradores/imunologia , Receptores Toll-Like/imunologia
15.
PLoS Pathog ; 13(12): e1006785, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29253868

RESUMO

Bacterial pathogens that compromise phagosomal membranes stimulate inflammasome assembly in the cytosol, but the molecular mechanisms by which membrane dynamics regulate inflammasome activity are poorly characterized. We show that in murine dendritic cells (DCs), the endosomal adaptor protein AP-3 -which optimizes toll-like receptor signaling from phagosomes-sustains inflammasome activation by particulate stimuli. AP-3 independently regulates inflammasome positioning and autophagy induction, together resulting in delayed inflammasome inactivation by autophagy in response to Salmonella Typhimurium (STm) and other particulate stimuli specifically in DCs. AP-3-deficient DCs, but not macrophages, hyposecrete IL-1ß and IL-18 in response to particulate stimuli in vitro, but caspase-1 and IL-1ß levels are restored by silencing autophagy. Concomitantly, AP-3-deficient mice exhibit higher mortality and produce less IL-1ß, IL-18, and IL-17 than controls upon oral STm infection. Our data identify a novel link between phagocytosis, inflammasome activity and autophagy in DCs, potentially explaining impaired antibacterial immunity in AP-3-deficient patients.


Assuntos
Complexo 3 de Proteínas Adaptadoras/deficiência , Células Dendríticas/imunologia , Células Dendríticas/microbiologia , Inflamassomos/imunologia , Imunidade Adaptativa , Complexo 3 de Proteínas Adaptadoras/genética , Complexo 3 de Proteínas Adaptadoras/imunologia , Animais , Autofagia/imunologia , Células Dendríticas/patologia , Feminino , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Interleucina-17/biossíntese , Interleucina-18/biossíntese , Interleucina-1beta/biossíntese , Interleucina-1beta/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas NLR/genética , Proteínas NLR/imunologia , Fagocitose , Salmonelose Animal/imunologia , Salmonelose Animal/patologia , Salmonella typhimurium/imunologia , Salmonella typhimurium/patogenicidade , Ativação Transcricional
17.
Med Mycol J ; 58(3): J83-J90, 2017.
Artigo em Japonês | MEDLINE | ID: mdl-28855484

RESUMO

Cryptococcus neoformans is a yeast-type opportunistic fungal pathogen with a capsule structure consisting of polysaccharides, such as glucuronoxylomannan and galactoxylomannan, and infects the lungs via an air-borne route. Most healthy individuals undergo asymptomatic infection with granulomatous lesions in the lungs caused by C. neoformans. However, immunocompromised hosts with severely impaired cellular immunity, such as those with acquired immune deficiency syndrome (AIDS), often suffer from disseminated infection into the central nervous system, leading to life-threatening meningoencephalitis. The recognition of pathogen-associated molecular patterns (PAMPs) by macrophages and dendritic cells plays an important role as the first line of host defense in the elimination of pathogens. Recently, numerous pattern recognition receptors (PRRs) that recognize these PAMPs have been identified. Also, the involvement of these PRRs, such as Toll-like receptors (TLRs), NOD-like receptors (NLRs), and C-type lectin receptors (CLRs), in cryptococcal infection has been analyzed. In particular, TLR9, NLR family pyrin domain-containing 3 (NLRP3), Dectin-2, mannose receptor (MR), and DC-SIGN have been found to recognize the DNA, cell wall components, intracellular polysaccharides, and mannoproteins, respectively. Future studies are expected to promote elucidation of the mechanisms of host immune response to C. neoformans, which will lead to the development of new vaccines and therapies for cryptococcal infection.


Assuntos
Criptococose/imunologia , Cryptococcus neoformans/imunologia , Padrões Moleculares Associados a Patógenos/imunologia , Receptores de Reconhecimento de Padrão/imunologia , Parede Celular/imunologia , Cryptococcus neoformans/química , Cryptococcus neoformans/citologia , Cryptococcus neoformans/genética , DNA Fúngico/imunologia , Polissacarídeos Fúngicos/imunologia , Vacinas Fúngicas , Humanos , Hospedeiro Imunocomprometido , Lectinas Tipo C/imunologia , Glicoproteínas de Membrana/imunologia , Proteínas NLR/imunologia , Receptores Toll-Like/imunologia
18.
Proc Natl Acad Sci U S A ; 114(35): E7385-E7394, 2017 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-28808003

RESUMO

Plants evolved intracellular immune receptors that belong to the NOD-like receptor (NLR) family to recognize the presence of pathogen-derived effector proteins. NLRs possess an N-terminal Toll-like/IL-1 receptor (TIR) or a non-TIR domain [some of which contain coiled coils (CCs)], a central nucleotide-binding (NB-ARC) domain, and a C-terminal leucine-rich repeat (LRR). Activation of NLR proteins results in a rapid and high-amplitude immune response, eventually leading to host cell death at the infection site, the so-called hypersensitive response. Despite their important contribution to immunity, the exact mechanisms of NLR activation and signaling remain unknown and are likely heterogenous. We undertook a detailed structure-function analysis of the plasma membrane (PM)-localized CC NLR Resistance to Pseudomonas syringae pv. maculicola 1 (RPM1) using both stable transgenic Arabidopsis and transient expression in Nicotiana benthamiana We report that immune signaling is induced only by activated full-length PM-localized RPM1. Our interaction analyses demonstrate the importance of a functional P-loop for in planta interaction of RPM1 with the small host protein RPM1-interacting protein 4 (RIN4), for constitutive preactivation and postactivation self-association of RPM1 and for proper PM localization. Our results reveal an additive effect of hydrophobic conserved residues in the CC domain for RPM1 function and RPM1 self-association and their necessity for RPM1-RIN4 interaction. Thus, our findings considerably extend our understanding of the mechanisms regulating NLR activation at, and signaling from, the PM.


Assuntos
Proteínas de Arabidopsis/imunologia , Proteínas de Arabidopsis/metabolismo , Imunidade Vegetal/imunologia , Sequência de Aminoácidos , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/fisiologia , Proteínas de Bactérias/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Membrana Celular/metabolismo , Imunidade Inata/imunologia , Proteínas NLR/imunologia , Doenças das Plantas/imunologia , Ligação Proteica , Pseudomonas syringae/fisiologia , Receptores Imunológicos/metabolismo , Transdução de Sinais , Tabaco/metabolismo
19.
Am J Physiol Heart Circ Physiol ; 313(5): H1000-H1012, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28801521

RESUMO

Aging is associated with chronic inflammation partly mediated by increased levels of damage-associated molecular patterns, which activate pattern recognition receptors (PRRs) of the innate immune system. Furthermore, many aging-related disorders are associated with inflammation. PRRs, such as Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain-like receptors (NLRs), are expressed not only in cells of the innate immune system but also in other cells, including cells of the neurovascular unit and cerebral vasculature forming the blood-brain barrier. In this review, we summarize our present knowledge about the relationship between activation of PRRs expressed by cells of the neurovascular unit-blood-brain barrier, chronic inflammation, and aging-related pathologies of the brain. The most important damage-associated molecular pattern-sensing PRRs in the brain are TLR2, TLR4, and NLR family pyrin domain-containing protein-1 and pyrin domain-containing protein-3, which are activated during physiological and pathological aging in microglia, neurons, astrocytes, and possibly endothelial cells and pericytes.


Assuntos
Envelhecimento/metabolismo , Barreira Hematoencefálica/metabolismo , Inflamassomos/metabolismo , Inflamação/metabolismo , Microvasos/metabolismo , Acoplamento Neurovascular , Receptores de Reconhecimento de Padrão/metabolismo , Transdução de Sinais , Fatores Etários , Envelhecimento/imunologia , Animais , Barreira Hematoencefálica/imunologia , Barreira Hematoencefálica/fisiopatologia , Humanos , Imunidade Inata , Inflamassomos/imunologia , Inflamação/imunologia , Inflamação/fisiopatologia , Microvasos/imunologia , Microvasos/fisiopatologia , Proteínas NLR/imunologia , Proteínas NLR/metabolismo , Receptores de Reconhecimento de Padrão/imunologia , Receptor 2 Toll-Like/imunologia , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/imunologia , Receptor 4 Toll-Like/metabolismo
20.
PLoS One ; 12(4): e0175336, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28403163

RESUMO

Inflammasomes are multiprotein complexes nucleating around an NLR (Nucleotide-binding domain and Leucine-rich Repeat containing protein), which regulate the secretion of the pro-inflammatory interleukin (IL)-1ß and IL-18 cytokines. Monocytes and macrophages, the main cells expressing the inflammasome genes, adapt to their surrounding microenvironment by a phenotypic polarization towards a pro-inflammatory M1 phenotype that promotes inflammation or an anti-inflammatory M2 phenotype important for resolution of inflammation. Despite the importance of inflammasomes in health and disease, little is known about inflammasome gene expression in relevant human cells and the impact of monocyte and macrophage polarization in inflammasome gene expression. We examined the expression of several members of the NLR, caspase and cytokine family, and we studied the activation of the well-described NLRP3 inflammasome in an experimental model of polarized human primary monocytes and monocyte-derived macrophages (M1/M2 phenotypes) before and after activation with LPS, a well-characterized microbial pattern used in inflammasome activation studies. Our results show that the differentiation of monocytes to macrophages alters NLR expression. Polarization using IFN-γ (M1 phenotype), induces among the NLRs studied, only the expression of NOD2. One of the key results of our study is that the induction of NLRP3 expression by LPS is inhibited in the presence of IL-4+IL-13 (M2 phenotype) at both mRNA and protein level in monocytes and macrophages. Unlike caspase-3, the expression of inflammasome-related CASP1 (encodes caspase-1) and CASP4 (encodes caspase-4) is up-regulated in M1 but not in M2 cells. Interestingly, the presence of LPS marginally influenced IL18 mRNA expression and secretion, unlike its impact on IL1B. Our data provide the basis for a better understanding of the role of different inflammasomes within a given environment (M1 and M2) in human cells and their impact in the pathophysiology of several important inflammatory disorders.


Assuntos
Inflamassomos/imunologia , Macrófagos/imunologia , Monócitos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Proteínas NLR/imunologia , Proteína Adaptadora de Sinalização NOD2/imunologia , Caspases/genética , Caspases/imunologia , Polaridade Celular , Células Cultivadas , Citocinas/genética , Citocinas/imunologia , Regulação da Expressão Gênica , Humanos , Inflamassomos/genética , Lipopolissacarídeos/imunologia , Macrófagos/citologia , Macrófagos/metabolismo , Monócitos/citologia , Monócitos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteínas NLR/genética , Proteína Adaptadora de Sinalização NOD2/genética
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