scholarly journals Specific modulation of the root immune system by a community of commensal bacteria

2021 ◽  
Vol 118 (16) ◽  
pp. e2100678118
Author(s):  
Paulo J. P. L. Teixeira ◽  
Nicholas R. Colaianni ◽  
Theresa F. Law ◽  
Jonathan M. Conway ◽  
Sarah Gilbert ◽  
...  
Keyword(s):  
Immune System ◽  
Commensal Bacteria ◽  
Immunomodulatory Activity ◽  
Specific Cell ◽  
Bacterial Flagellum ◽  
Surface Receptors ◽  
Evolutionarily Conserved ◽  
Type 3 Secretion System ◽  
Molecular Patterns ◽  
Type 3

Plants have an innate immune system to fight off potential invaders that is based on the perception of nonself or modified-self molecules. Microbe-associated molecular patterns (MAMPs) are evolutionarily conserved microbial molecules whose extracellular detection by specific cell surface receptors initiates an array of biochemical responses collectively known as MAMP-triggered immunity (MTI). Well-characterized MAMPs include chitin, peptidoglycan, and flg22, a 22-amino acid epitope found in the major building block of the bacterial flagellum, FliC. The importance of MAMP detection by the plant immune system is underscored by the large diversity of strategies used by pathogens to interfere with MTI and that failure to do so is often associated with loss of virulence. Yet, whether or how MTI functions beyond pathogenic interactions is not well understood. Here we demonstrate that a community of root commensal bacteria modulates a specific and evolutionarily conserved sector of the Arabidopsis immune system. We identify a set of robust, taxonomically diverse MTI suppressor strains that are efficient root colonizers and, notably, can enhance the colonization capacity of other tested commensal bacteria. We highlight the importance of extracellular strategies for MTI suppression by showing that the type 2, not the type 3, secretion system is required for the immunomodulatory activity of one robust MTI suppressor. Our findings reveal that root colonization by commensals is controlled by MTI, which, in turn, can be selectively modulated by specific members of a representative bacterial root microbiota.

Role of Toll-like receptors in liver health and disease

2011 ◽  
Vol 121 (10) ◽  
pp. 415-426 ◽  
Author(s):  
Ruth Broering ◽  
Mengji Lu ◽  
Joerg F. Schlaak
Keyword(s):  
Immune System ◽  
Liver Disease ◽  
Innate Immune System ◽  
Innate Immune ◽  
Toll Like Receptors ◽  
Evolutionarily Conserved ◽  
Liver Health ◽  
Health And Disease ◽  
Molecular Patterns

TLRs (Toll-like receptors), as evolutionarily conserved germline-encoded pattern recognition receptors, have a crucial role in early host defence by recognizing so-called PAMPs (pathogen-associated molecular patterns) and may serve as an important link between innate and adaptive immunity. In the liver, TLRs play an important role in the wound healing and regeneration processes, but they are also involved in the pathogenesis and progression of various inflammatory liver diseases, including autoimmune liver disease, alcoholic liver disease, non-alcoholic steatohepatitis, fibrogenesis, and chronic HBV (hepatitis B virus) and HCV (hepatitis C virus) infection. Hepatitis viruses have developed different evading strategies to subvert the innate immune system. Thus recent studies have suggested that TLR-based therapies may represent a promising approach in the treatment in viral hepatitis. The present review focuses on the role of the local innate immune system, and TLRs in particular, in the liver.

scholarly journals In Vivo Discrimination of Type 3 Secretion System-Positive and -Negative Pseudomonas aeruginosa via a Caspase-1-Dependent Pathway

2010 ◽  
Vol 78 (11) ◽  
pp. 4744-4753 ◽  
Author(s):  
Tamding Wangdi ◽  
Lilia A. Mijares ◽  
Barbara I. Kazmierczak
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Immune System ◽  
Innate Immune System ◽  
Interleukin 1 ◽  
Innate Immune ◽  
Secretion Systems ◽  
Caspase 1 ◽  
Molecular Patterns ◽  
Type 3

ABSTRACT Microbe-associated molecular patterns are recognized by Toll-like receptors of the innate immune system. This recognition enables a rapid response to potential pathogens but does not clearly provide a way for the innate immune system to discriminate between virulent and avirulent microbes. We find that pulmonary infection of mice with type 3 translocation-competent Pseudomonas aeruginosa triggers a rapid inflammatory response, while infection with isogenic translocation-deficient mutants does not. Discrimination between translocon-positive and -negative bacteria requires caspase-1 activity in bone marrow-derived cells and interleukin-1 receptor signaling. Thus, the activation of caspase-1 by bacteria expressing type 3 secretion systems allows for rapid recognition of bacteria expressing conserved functions associated with virulence.

scholarly journals Innovation in NLR and TLR sensing drives the MHC-II free Atlantic cod immune system

2020 ◽  
Author(s):  
Xingkun Jin ◽  
Bernat Morro ◽  
Ole K. Tørresen ◽  
Visila Moiche ◽  
Monica H. Solbakken ◽  
...  
Keyword(s):  
Immune System ◽  
Mhc Class Ii ◽  
Atlantic Cod ◽  
Ex Vivo ◽  
Specific Cell ◽  
Major Response ◽  
History Of ◽  
Underlying Mechanisms ◽  
Molecular Patterns ◽  
Cluster Of Differentiation

AbstractThe genome sequencing of Atlantic cod revealed an immune system absent of specific cell surface toll-like receptors (TLRs), major histocompatibility complex (MHC) class II, invariant chain (CD74) and the CD4 (cluster of differentiation 4) receptor. Despite the loss of these major components considered as critical to vertebrate innate and adaptive immune systems the cod system is fully functional, however the underlying mechanisms of the immune response in cod remain largely unknown. In this study, ex vivo cod macrophages were challenged with various bacterial and viral microbe-associated molecular patterns (MAMP) to identify major response pathways. Cytosolic MAMP-PRR pathways based upon the NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs) were identified as the critical response pathways. Our analyses suggest that internalization of exogenous ligands through scavenger receptors drives both pathways activating transcription factors like NF-kB (Nuclear factor-kappa B) and interferon regulatory factors (IRFs). Further, ligand-dependent differential expression of a unique TLR25 isoform and multiple NLR paralogues suggests (sub)neofunctionalisation toward specific immune defensive strategies. Our results further demonstrate that the unique immune system of the Atlantic cod provides an unprecedented opportunity to explore the evolutionary history of PRR-based signalling in vertebrate immunity.

scholarly journals Response of Pseudomonas aeruginosa to the Innate Immune System-Derived Oxidants Hypochlorous Acid and Hypothiocyanous Acid

2020 ◽  
Vol 203 (2) ◽  
pp. e00300-20
Author(s):  
Katie V. Farrant ◽  
Livia Spiga ◽  
Jane C. Davies ◽  
Huw D. Williams
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Immune System ◽  
Hypochlorous Acid ◽  
Secretion System ◽  
Content Type ◽  
Type 3 Secretion System ◽  
Lung Infections ◽  
Type 3

ABSTRACTPseudomonas aeruginosa is a significant nosocomial pathogen and is associated with lung infections in cystic fibrosis (CF). Once established, P. aeruginosa infections persist and are rarely eradicated despite host immune cells producing antimicrobial oxidants, including hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN). There is limited knowledge as to how P. aeruginosa senses, responds to, and protects itself against HOCl and HOSCN and the contribution of such responses to its success as a CF pathogen. To investigate the P. aeruginosa response to these oxidants, we screened 707 transposon mutants, with mutations in regulatory genes, for altered growth following HOCl exposure. We identified regulators of antibiotic resistance, methionine biosynthesis, catabolite repression, and PA14_07340, the homologue of the Escherichia coli HOCl-sensor RclR (30% identical), which are required for protection against HOCl. We have shown that RclR (PA14_07340) protects specifically against HOCl and HOSCN stress and responds to both oxidants by upregulating the expression of a putative peroxiredoxin, rclX (PA14_07355). Transcriptional analysis revealed that while there was specificity in the response to HOCl (231 genes upregulated) and HOSCN (105 genes upregulated), there was considerable overlap, with 74 genes upregulated by both oxidants. These included genes encoding the type 3 secretion system, sulfur and taurine transport, and the MexEF-OprN efflux pump. RclR coordinates part of the response to both oxidants, including upregulation of pyocyanin biosynthesis genes, and, in the presence of HOSCN, downregulation of chaperone genes. These data indicate that the P. aeruginosa response to HOCl and HOSCN is multifaceted, with RclR playing an essential role.IMPORTANCE The bacterial pathogen Pseudomonas aeruginosa causes devastating infections in immunocompromised hosts, including chronic lung infections in cystic fibrosis patients. To combat infection, the host’s immune system produces the antimicrobial oxidants hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN). Little is known about how P. aeruginosa responds to and survives attack from these oxidants. To address this, we carried out two approaches: a mutant screen and transcriptional study. We identified the P. aeruginosa transcriptional regulator, RclR, which responds specifically to HOCl and HOSCN stress and is essential for protection against both oxidants. We uncovered a link between the P. aeruginosa transcriptional response to these oxidants and physiological processes associated with pathogenicity, including antibiotic resistance and the type 3 secretion system.

scholarly journals Combinational clustering of receptors following stimulation by bacterial products determines lipopolysaccharide responses

2004 ◽  
Vol 381 (2) ◽  
pp. 527-536 ◽  
Author(s):  
Martha TRIANTAFILOU ◽  
Klaus BRANDENBURG ◽  
Shoichi KUSUMOTO ◽  
Koichi FUKASE ◽  
Alan MACKIE ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Innate Immune System ◽  
Imaging Techniques ◽  
Innate Immune ◽  
Surface Receptors ◽  
Wide Range ◽  
Species Specific ◽  
Receptor Clusters ◽  
Molecular Patterns

The innate immune system has the capacity to recognize a wide range of pathogens based on conserved PAMPs (pathogen-associated molecular patterns). In the case of bacterial LPS (lipopolysaccharide) recognition, the best studied PAMP, it has been shown that the innate immune system employs at least three cell-surface receptors: CD14, TLR4 (Toll-like receptor 4) and MD-2 protein. CD14 binds LPS from Enterobacteriaceae and then transfers it to MD-2, leading to TLR4 aggregation and signal transduction. LPS analogues such as lipid IVa seem to act as LPS antagonists in human cells, but exhibit LPS mimetic activity in mouse cells. Although TLR4 has been shown to be involved in this species-specific discrimination, the mechanism by which this is achieved has not been elucidated. The questions that remain are how the innate immune system can discriminate between LPS from different bacteria as well as different LPS analogues, and whether or not the structure of LPS affects its interaction with the CD14–TLR4–MD-2 cluster. Is it possible that the ‘shape’ of LPS induces the formation of different receptor clusters, and thus a different immune response? In the present study, we demonstrate using biochemical as well as fluorescence-imaging techniques that different LPS analogues trigger the recruitment of different receptors within microdomains. The composition of each receptor cluster as well as the number of TLR4 molecules that are recruited within the cluster seem to determine whether an immune response will be induced or inhibited.

scholarly journals Pathogen Recognition by the Long Pentraxin PTX3

2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Federica Moalli ◽  
Sebastien Jaillon ◽  
Antonio Inforzato ◽  
Marina Sironi ◽  
Barbara Bottazzi ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Immune System ◽  
Innate Immune System ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Pathogen Recognition ◽  
Evolutionarily Conserved ◽  
Infection And Inflammation ◽  
Molecular Patterns

Innate immunity represents the first line of defence against pathogens and plays key roles in activation and orientation of the adaptive immune response. The innate immune system comprises both a cellular and a humoral arm. Components of the humoral arm include soluble pattern recognition molecules (PRMs) that recognise pathogen-associated molecular patterns (PAMPs) and initiate the immune response in coordination with the cellular arm, therefore acting as functional ancestors of antibodies. The long pentraxin PTX3 is a prototypic soluble PRM that is produced at sites of infection and inflammation by both somatic and immune cells. Gene targeting of this evolutionarily conserved protein has revealed a nonredundant role in resistance to selected pathogens. Moreover, PTX3 exerts important functions at the cross-road between innate immunity, inflammation, and female fertility. Here, we review the studies on PTX3, with emphasis on pathogen recognition and cross-talk with other components of the innate immune system.

scholarly journals The Structure of a Type 3 Secretion System (T3SS) Ruler Protein Suggests a Molecular Mechanism for Needle Length Sensing

2015 ◽  
Vol 291 (4) ◽  
pp. 1676-1691 ◽  
Author(s):  
Julien R. C. Bergeron ◽  
Lucia Fernández ◽  
Gregory A. Wasney ◽  
Marija Vuckovic ◽  
Fany Reffuveille ◽  
...  
Keyword(s):  
Secretion System ◽  
Globular Domain ◽  
Tubular Structures ◽  
Needle Length ◽  
Bacterial Flagellum ◽  
Bacterial Surface ◽  
Intrinsically Disordered ◽  
Cytosolic Side ◽  
Type 3 Secretion System ◽  
Type 3

The type 3 secretion system (T3SS) and the bacterial flagellum are related pathogenicity-associated appendages found at the surface of many disease-causing bacteria. These appendages consist of long tubular structures that protrude away from the bacterial surface to interact with the host cell and/or promote motility. A proposed “ruler” protein tightly regulates the length of both the T3SS and the flagellum, but the molecular basis for this length control has remained poorly characterized and controversial. Using the Pseudomonas aeruginosa T3SS as a model system, we report the first structure of a T3SS ruler protein, revealing a “ball-and-chain” architecture, with a globular C-terminal domain (the ball) preceded by a long intrinsically disordered N-terminal polypeptide chain. The dimensions and stability of the globular domain do not support its potential passage through the inner lumen of the T3SS needle. We further demonstrate that a conserved motif at the N terminus of the ruler protein interacts with the T3SS autoprotease in the cytosolic side. Collectively, these data suggest a potential mechanism for needle length sensing by ruler proteins, whereby upon T3SS needle assembly, the ruler protein's N-terminal end is anchored on the cytosolic side, with the globular domain located on the extracellular end of the growing needle. Sequence analysis of T3SS and flagellar ruler proteins shows that this mechanism is probably conserved across systems.

scholarly journals PSVI-5 Rumen-protected methionine supplementation during the peripartal period reduces the expression of LGALS-1, -3 and -4 in polymorphonuclear leukocytes (PMNL) and secretion of Gal-2 and Gal-12 in plasma of Holstein cows

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 200-201
Author(s):  
Emmanuel K Asiamah ◽  
Mulumebet Worku ◽  
Juan Loor ◽  
Mario Vailati Riboni ◽  
Zheng Zhou ◽  
...  
Keyword(s):  
Signaling Cascades ◽  
Holstein Cows ◽  
Dietary Interventions ◽  
Surface Receptors ◽  
Periparturient Period ◽  
Evolutionarily Conserved ◽  
Genes Encoding ◽  
Methionine Supplementation ◽  
Improved Function ◽  
Molecular Patterns

Abstract The objective of this study was to evaluate the effect of methionine(Met) supplementation on genes encoding Galectins (LGALS) and secretion in plasma during the periparturient period. Dairy cows are susceptible to increased incidence and severity of disease during the periparturient period. Impaired polymorphonuclear leukocyte (PMNL) functions such as phagocytosis and pathogen killing capacity contribute to immune dysfunction and disease. Galectins (GALS) are an evolutionarily conserved family of animal lectins important in disease and homeostasis. They behave like pathogen-associated molecular patterns and cell-surface receptors whose activation often results in signaling cascades to activate cells such as PMNL. Fourteen Holstein cows supplemented with either rumen-protected Met (n = 7) or no Met (CON; n = 7) were used. Diets were fed from −21 ± 2 before expected calving date and continued until 30 days postpartum. To evaluate LGALS expression and secretion of Gal, PMNL were isolated from blood and plasma was harvested at -10, +7, and +30 d relative to expected calving. The expression of LGALS1 (P = 0.09), LGALS3 (P = 0.02), and LGALS4 (P = 0.02) was lower in response to Met, but there was no effect on LGALS8, LGALS9, and LGALS12. Met supplementation reduced Gal-2 and Gal-12 secretion in plasma at -10, +7, and +30 d (P < 0.0005 and P < 0.0001 respectively). Methionine supplementation modulates the expression of GAL involved in inflammation and lipolysis in cow blood. Modulation of GAL in PMNL and plasma in response to Met may have implications for the use of dietary interventions to target gene expression in PMNL for improved function and needs further study.

Nanotheranostic agents for neurodegenerative diseases

2020 ◽  
Vol 4 (6) ◽  
pp. 645-675
Author(s):  
Parasuraman Padmanabhan ◽  
Mathangi Palanivel ◽  
Ajay Kumar ◽  
Domokos Máthé ◽  
George K. Radda ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Neurodegenerative Diseases ◽  
Cell Types ◽  
Specific Cell ◽  
Ageing Population ◽  
Target Tissue ◽  
Therapeutic Approaches ◽  
Surface Receptors ◽  
Theranostic Agents ◽  
Preclinical Animal Models

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), affect the ageing population worldwide and while severely impairing the quality of life of millions, they also cause a massive economic burden to countries with progressively ageing populations. Parallel with the search for biomarkers for early detection and prediction, the pursuit for therapeutic approaches has become growingly intensive in recent years. Various prospective therapeutic approaches have been explored with an emphasis on early prevention and protection, including, but not limited to, gene therapy, stem cell therapy, immunotherapy and radiotherapy. Many pharmacological interventions have proved to be promising novel avenues, but successful applications are often hampered by the poor delivery of the therapeutics across the blood-brain-barrier (BBB). To overcome this challenge, nanoparticle (NP)-mediated drug delivery has been considered as a promising option, as NP-based drug delivery systems can be functionalized to target specific cell surface receptors and to achieve controlled and long-term release of therapeutics to the target tissue. The usefulness of NPs for loading and delivering of drugs has been extensively studied in the context of NDDs, and their biological efficacy has been demonstrated in numerous preclinical animal models. Efforts have also been made towards the development of NPs which can be used for targeting the BBB and various cell types in the brain. The main focus of this review is to briefly discuss the advantages of functionalized NPs as promising theranostic agents for the diagnosis and therapy of NDDs. We also summarize the results of diverse studies that specifically investigated the usage of different NPs for the treatment of NDDs, with a specific emphasis on AD and PD, and the associated pathophysiological changes. Finally, we offer perspectives on the existing challenges of using NPs as theranostic agents and possible futuristic approaches to improve them.

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