Balanced immune responses in airways of patients with asthma are crucial to succesful clearance of viral infection and proper asthma control.
Rhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19.
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View SamplesIn order to better understand the systemic immunological responses in a clinical cohort of obese and non-obese asthmatics and healthy subjects, we sought to analyze gene expression from whole blood. We collected whole blood samples from 156 donors and performed gene expression analysis of these samples and identified differentially expressed genes (DEGs) in each obese and/or asthma group relative to healthy volunteers.
Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients.
Sex, Age, Specimen part, Subject
View SamplesWe have begun to approach gd T cells more as prospective innate cells than as conventional T cells. Recent results indicated that purified gd T cells are primed directly in response to pathogen associated molecular patterns (PAMPs) to better respond to secondary signals and increase expression of chemokine and activation-related genes. In microarray and real time PCR analyses of RNA derived from bovine and human gd T cells, transcripts encoding Nod2 were repeatedly amplified. Nod2 is the intracellular receptor for muramyl dipeptide (MDP), a subunit of PGN, functions in regulating innate activities, and was thought to be expressed primarily in APCs. Given our repeated detection of Nod2 transcripts in gd T cells, the specific direct response of gd T cells to MDP was analyzed by microarray, real time PCR, proteome array and in a functional priming assay. The results indicate a subtle activation in response to MDP akin to priming, and suggest a unique mechanism for differential gene expression.
The distinct response of gammadelta T cells to the Nod2 agonist muramyl dipeptide.
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View Samplesgd T cells recognize unprocessed or non-peptide antigens, respond rapidly to infection, and localize to mucosal surfaces. We have hypothesized that the innate functions of gd T cells may be more similar to those of cells of the myeloid lineage than to other T cells. To begin to test this assumption, we have analyzed the direct response of cultured human and peripheral blood bovine gd T cells to pathogen associated molecular patterns (PAMPs) in the absence of APCs using microarray, real time RT-PCR, proteome array, and chemotaxis assays. Our results indicate that purified gd T cells respond directly to PAMPs by increasing expression of chemokine and activation related genes. The response was distinct from that to known gd T cell antigens and different from the response of myeloid cells to PAMPs. In addition, we have analyzed the expression of a variety of PAMP receptors in gd T cells. Freshly purified bovine gd T cells responded more robustly to PAMPs than did cultured human cells and expressed measurable mRNA encoding a variety of PAMP receptors. Our results suggest that rapid response to PAMPs through the expression of PAMP receptors may be another innate role of gd T cells.
Gamma delta T cells respond directly to pathogen-associated molecular patterns.
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View SamplesYamoa is marketed and sold as a dietary supplement with anecdotal positive effects in asthma and hay fever. We determined that Yamoa (ground bark of Funtumia elastica tree) stimulated innate immunity in part by affecting gamma delta T cells. Yamoa had distinct priming effects, very similar to, but more robust than, that of lipopolysaccharide (LPS), on bovine, mouse and human gamma delta T cells. However, the optimal effect was dependent on the presence of accessory cells. Gene expression patterns in bovine gamma delta T cells and monocytes induced by Yamoa were very similar to those induced by ultrapure LPS, but the agonists in Yamoa did not signal entirely through TLR4. Yamoa stimulated human cells to produce cytokines involved innate protection. The bioactive component of Yamoa was delineated to a complex polysaccharide fraction (Yam-I). Intraperitoneal injection of Yamoa and very low doses of Yam-I in mice induced rapid increases peritoneal neutrophils directed by changes chemokine expression. Yamoa and Yam-I were effective as therapeutic treatments in mice with Salmonella enterica serotype Typhimurium (ST) induced enterocolitis that resulted in decreased bacterial counts in feces. This initial characterization of the immune stimulatory properties of polysaccharides derived from Yamoa suggests potential mechanisms for positive effects in asthma and that they have potential for application in infectious disease settings. .
Polysaccharides derived from Yamoa (Funtumia elastica) prime gammadelta T cells in vitro and enhance innate immune responses in vivo.
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