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Whole blood gene expression after stimulation with TLR2 ligands (chitin oligomers, Pam2, Pam3) and the TLR4-ligand LPS

ABSTRACT: Chitin is the second most abundant polysaccharide in nature and a biomolecule intimately linked to fungal infection and allergic asthma, conditions that affect millions of patients worldwide. Chitin is known to stimulate multiple mammalian immune cells, but the precise molecular sensing mechanism has not been elucidated, hampering strategies to specifically target chitin-mediated pathologies. The study associated with this microarray dataset uses defined chitin oligomers to identify six chitin subunits as the smallest immunologically active chitin motif and the innate immune receptor TLR2 as the molecular chitin sensor on human and murine immune cells, in vitro and in vivo. The goal of this microarray dataset was to elucidate transcriptional differences of human whole blood cells when responding to chitin, to other TLR2 ligands (Pam2, Pam3), and furthermore to the TLR4 ligand LPS. All four stimulants are compared to each other and to the unstimulated whole blood samples as a reference. We conclude that chitin oligomers elicitd overlapping yet distinct signaling outcomes compared to canonical TLR2 ligands.

ORGANISM(S): Homo sapiens

PROVIDER: GSE103094 | GEO | 2018/03/07

REPOSITORIES: GEO

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The immune receptor TLR2 directly binds and signals immune activation to oligomeric chitin

Project description:Chitin is the second most abundant polysaccharide in nature and a biomolecule intimately linked to fungal infection and allergic asthma, conditions that affect millions of patients worldwide. Chitin is known to stimulate multiple mammalian immune cells, but the precise molecular sensing mechanism has not been elucidated, hampering strategies to specifically target chitin-mediated pathologies. Using defined chitin oligomers we here identify six chitin subunits as the smallest immunologically active chitin motif and the innate immune receptor TLR2 as the molecular chitin sensor on human and murine immune cells, in vitro and in vivo. Chitin oligomers directly bound TLR2 with nanomolar affinity and elicited overlapping yet distinct signaling outcomes compared to canonical TLR2 ligands. Conversely, chitin oligomers composed of five chitin subunits acted as antagonists of chitin-TLR2 immune activation, hinting to an anti-inflammatory loop already known from plants, to also operate in humans. Of note, small chitin oligomers and biological-based blocking of the TLR2-chitin interaction effectively prevented chitin-mediated inflammation not only in vitro but also in vivo. Collectively, our study elucidates the molecular basis of how chitin is sensed by mammalian immune cells, which has broad impact for chitin-associated inflammatory pathologies. From a translational perspective, our findings further suggests that differently sized chitin oligomers could be developed into novel vaccine adjuvants or immuno-modulatory antagonists for the prevention or treatment of chitin-driven diseases in humans.

2019-11-12 | PXD007542 | Pride

Chitin elicitation timecourse

Project description:Chitin oligomers, released from fungal cell walls by endochitinase, induce defense and related cellular responses in many plants. However, little is known about chitin responses in the model plant Arabidopsis. We describe here a large scale characterization of gene expression patterns in Arabidopsis in response to chitin treatment using an Arabidopsis microarray consisting of 2,375 EST clones representing putative defense-related and regulatory genes. Transcript levels for 71 ESTs, representing 61 genes, were altered >3-fold in chitin-treated seedlings relative to control seedlings. A number of transcripts exhibited altered accumulation as early as 10 min after exposure to chitin, representing some of the earliest changes in gene expression observed in chitin-treated plants. Included among the 61 genes are those that have been reported to be elicited by various pathogen-related stimuli in other plants. Additional genes, including genes of unknown function, were also identified broadening our understanding of chitin-elicited responses. Among transcripts with enhanced accumulation, one cluster was enriched in genes with both the W-box promoter element and a novel regulatory element. In addition, a number of transcripts had decreased abundance, encoding several proteins involved in cell wall strengthening and wall deposition. The chalcone synthase promoter element was identified in the upstream regions of these genes, suggesting that pathogen signals may suppress expression of some genes. These data indicate that Arabidopsis will be an excellent model to elucidate mechanisms of chitin elicitation in plant defense. Groups of assays that are related as part of a time series. Keywords: time_series_design Computed

2005-09-09 | E-GEOD-3273 | biostudies-arrayexpress

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2005-09-09 | GSE3273 | GEO

Transcription profiling of Arabidopsis in response to chitin treatment

2005-09-02 | E-SMDB-1627 | biostudies-arrayexpress

Homo sapiens

Project description:Whole blood gene expression after stimulation with TLR2 ligands (chitin oligomers, Pam2, Pam3) and the TLR4-ligand LPS

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Chitin Oligomer Experiment

Project description:Using the ATH1 Affymetrix microarrays consisting of about 23,000 genes, we examined the response of Arabidopsis seedlings to chito-tetramers, chito-octamers and hydrolyzed chitin after 30 min of treatment. Keywords = chitin Keywords = defense Keywords = elicitor Keywords = mutant Keywords = powdery mildew Keywords = Erysiphe cichoracearum Keywords: ordered

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The Vibrio cholerae chitin utilization program

Project description:Abstract: Chitin, an insoluble polymer of GlcNAc, is an abundant source of carbon, nitrogen, and energy for marine microorganisms. Microarray expression profiling and mutational studies of Vibrio cholerae growing on a natural chitin surface, or with the soluble chitin oligosaccharides (GlcNAc)(2-6), GlcNAc, or the glucosamine dimer (GlcN)2 identified three sets of differentially regulated genes. We show that (i) ChiS, a sensor histidine kinase, regulates expression of the (GlcNAc)(2-6) gene set, including a (GlcNAc)2 catabolic operon, two extracellular chitinases, a chitoporin, and a PilA-containing type IV pilus, designated ChiRP (chitin-regulated pilus) that confers a significant growth advantage to V. cholerae on a chitin surface; (ii) GlcNAc causes the coordinate expression of genes involved with chitin chemotaxis and adherence and with the transport and assimilation of GlcNAc; (iii) (GlcN)2 induces genes required for the transport and catabolism of nonacetylated chitin residues; and (iv) the constitutively expressed MSHA pilus facilitates adhesion to the chitin surface independent of surface chemistry. Collectively, these results provide a global portrait of a complex, multistage V. cholerae program for the efficient utilization of chitin. This SuperSeries is composed of the SubSeries listed below.

2006-03-08 | GSE4388 | GEO

Chitin oligosaccharide-responsive genes in suspension-cultured rice cells

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2012-07-24 | E-GEOD-39633 | biostudies-arrayexpress

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Project description:Strain N16961 grown in M9 + 0.5 % lactate to OD 0.2. Culture was split and one part added 0.6 mM of indicated chitin oligosaccharide. Samples was isolated after 30 and 60 min. cDNA was prepared from 2 ug RNA and labeled with Cy3 (no induction) and Cy5 (induction with chitin oligosaccharide). Samples from at least two independent experiments and a total of four hybridizations for each chitin oligosaccharide and time. A growth condition experiment design type is where some part of the growth condition is changed for the purposes of the experiment, examples of growth conditions changed are media, temperature, humidity, light, nutrients. Keywords: growth_condition_design

2005-08-11 | GSE3101 | GEO

Chitin oligosaccharide elicitor-responsive genes in suspension cultured rice cells

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2014-04-01 | E-GEOD-53414 | biostudies-arrayexpress

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