Generation of immune-enhancing neutrophils by subclinical super-low dose LPS
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ABSTRACT:
PROVIDER: PRJNA958103 | ENA |
REPOSITORIES: ENA
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Project description:We have generated immune-enhancing neutrophils by culturing murine primary bone marrow derived neutrophils with either super-low dose of LPS. Immune-enhancing neutrophils preferentially express co-stimulatory molecules such as CD74, CD44 and CD86, and exhibit reduced expression of CD11b. Purified bone marrow neutrophils were treated with PBS or 100 pg/ml LPS overnight in the presence of GM-CSF, and harvested for scRNAseq analysis to examine their profiles of gene expression.
2024-05-17 | GSE230237 | GEO
Project description:We have performed analyses of murine primary bone marrow derived neutrophils challenged with either ultra-low dose or high dose of LPS. Neutrophils can be differentially programmed to distinct states by varying dosages of LPS. Purified bone marrow neutrophils were treated with PBS, 100 pg/ml LPS or 100 ng/ml LPS overnight, and harvested for scRNAseq analysis to examine their profiles of gene expression.
2023-12-27 | GSE230241 | GEO
Project description:Dose dependent reprogramming of neutrophils by LPS
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Project description:Despite the re-emergence of the pioneering "Coley's toxin" concept in anti-cancer immune therapies highlighted by check-point inhibitors and CAR-T approaches, fundamental mechanisms responsible for the immune-enhancing efficacy of low-dose "Coley's toxin" remain poorly understood. This study examines the novel reprogramming of immune-enhancing neutrophils by super-low dose endotoxin conducive for anti-cancer therapies. Through integrated analyses including scRNAseq and functional characterizations, we examined the efficacy of reprogrammed neutrophils in treating experimental cancer. We observed that neutrophils trained by super-low dose endotoxin adopt a potent immune-enhancing phenotype characterized by CD177loCD11bloCD80hiCD40hiDectin2hi. Both murine and human neutrophils trained by super-low dose endotoxin exhibit relieved suppression of adaptive T cells as compared to un-trained neutrophils. Functionally, neutrophils trained by super-low dose endotoxin can potently reduce tumor burden when transfused into recipient tumor-bearing mice. Mechanistically, Super-low dose endotoxin enables the generation of immune-enhancing neutrophils through activating STAT5 and reducing innate suppressor IRAK-M. Together, our data clarify the long-held mystery of "Coley's toxin" in rejuvenating anti-tumor immune defense, and provide a proof-of-concept in developing innate neutrophil-based anti-tumor therapeutics.
| S-SCDT-10_1038-S44321-024-00100-7 | biostudies-other
Project description:Post-partum uterine inflammation (endometritis) is associated with lower fertility at both the time of infection and after the inflammation has resolved. It was hypothesized that aberrant DNA methylation may be involved in the sub-fertility associated with post-partum uterine inflammation. The objective of this study was to characterize genome-wide DNA methylation and gene expression in the endometrium of dairy cows with sub-clinical endometritis. Endometrial tissues were obtained at 29 days post-partum (n=12) and Agilent two-colour microarrays were used to characterize transcription and DNA methylation profiles. Analyses revealed 1,856 probes to be differentially expressed in animals with subclinical endometritis (SUI, n=6) compared with control cows (NUI, n=6, P<0.05, Storey Multiple testing correction). No significant associations among DNA methylation and gene expression were detected. Further analysis of gene expression data using GeneGo Metacore and Gene Set Enrichment Analysis identified several pathways and processes enriched in the comparison. Several pathways that are involved in the innate immune response were enriched in SUI cows. Consistent with the presence of microorganisms in the uterus, there was enrichment for the Toll-like receptor (TLR) signaling pathway, including increased expression of the transcription factor NFKB1, the pro-inflammatory cytokines IL1A and IL1B, downstream chemokines, cytokines, and acute phase and antimicrobial proteins in the endometrium of SUI cows. Furthermore, the chemokine signaling pathway was enriched in SUI cows, with increased expression of genes that attract cells of the innate immune system. Increased expression of IL-8 and CXCL6, chemotactic factors for recruitment of neutrophils along with the immune cell surface marker PTPRC in SUI cows is consistent with the greater number of polymorphonuclear cells present in the uterus of these cows. Several antimicrobial peptides (LAP, TAP, DEFB1, DEFB10, DEFB103B, DEFB7) and acute phase proteins, including SAA3, LBP, and the complement gene CFB, had greater expression in SUI cows. Gene expression profiles in cows with subclinical endometritis in this study indicate that the immune response is activated, potentially resulting in a local pro-inflammatory environment in the uterus. If this period of inflammation is prolonged, it could result in tissue damage or failure to complete involution of the uterus, which may create a sub-optimal environment for future pregnancy. Agilent two-colour microarrays were used to characterize DNA methylation profiles in cows with subclinical endometritis (SUI, n=6) compared to control cows (NUI, n=6). Endometrial tissues (caruncular, intercaruncular) were obtained at 29 days post-partum.
2015-05-07 | E-GEOD-60831 | biostudies-arrayexpress
Project description:Clinical or subclinical endometritis could affect the cow fertility by disturbing the molecular milieu of the uterine environment. We used a global gene expression approach to understand the effect of clinical and subclinical endometritis on endometrial transcriptome profiles of cows
2016-11-13 | GSE74987 | GEO
Project description:Mastitis, the inflammation of the mammary gland, is one of the most prevalent diseases in dairy farming worldwide. Unfortunately, the disease is most often present in a subclinical type with no clear symptoms. The sooner the infection is detected, the less opportunities for the disease to progress and the more treatment options remain available. Milk microRNA (miRNA) encapsulated in extracellular vesicles (EV) have been proposed as potential biomarkers of different mammary gland conditions, including subclinical mastitis. However, little is known about the robustness of EV analysis regarding sampling time-point or natural infections. In order to estimate the reliability of EV measurements in raw bovine milk, we first evaluated the changes in EV size, concentration and miRNA cargo during three consecutive days. Then, we compared milk EV differences from natural infected quarters with high somatic cell count (SCC) with their healthy adjacent quarters with low SCC and quarters from uninfected udders. We found that milk EV miRNA cargo is very stable along three days and that infected quarters do not induce relevant changes in milk EV of adjacent healthy quarters, making them suitable controls. We observed cow-individual changes in immunoregulatory miRNA in quarters with chronic subclinical mastitis, pointing towards infection-specific alterations. Finally, we proposed bta-miR-223 as a potential indicator of subclinical mastitis prognosis in raw milk.
2022-03-16 | GSE149856 | GEO
Project description:Combining the cytological as well as gene expression changes in the endometrium is required to understand the effects of subclinical endometritis on endometrium as well as embryo. Hence, the present study was aimed to investigate the gene expression profiles of subclinical endometrium as well the effect of the inflamed environment on the gene expression profile of the developing preimplantative embryo.
2011-11-09 | GSE33496 | GEO
Project description:The aim of this study was to investigate correlations between early subclinical findings (10 and 90 day histology and gene expression data) and late outcomes (transplant glomerulopathy and graft loss) in positive crossmatch kidney transplants (+XMKTx).
2016-06-08 | GSE82337 | GEO
Project description:Milk microRNAs (miRNAs) encapsulated in extracellular vesicles (EVs) are a novel class of bioactive food compounds. Milk produced by cows with subclinical mastitis threatens animals healthy and milk safety. However, little is known about the differentially expressed miRNA in milk-derived EVs related to subclinical mastitis. This study profiled miRNAs in milk-derived EVs from healthy cows and cows with subclinical mastitis. The potential targets for differentially expressed (DE) miRNAs were predicted. Milk-derived EVs were isolated from healthy cows (n = 7, the control group) and cows with subclinical (n = 7, the SM group). Two hundred ninety miRNAs (221 known and 69 novel ones) were identified. The top 20 miRNAs were commonly abundant (> 0.1% of the total read counts) in Healthy and SM groups, were regarded as abundant bovine milk-derived EVs miRNAs. MiR-21-5p was the most highly expressed known miRNA. Target genes of the top 20 abundant miRNAs were significantly enriched in Ras signaling pathway. The bta-miR-21-5p, bta-miR-30a-5p and miR-6-1096 were differentially expressed. For DE miRNAs, there was no significantly enriched pathways were found in the KEGG enrichment analysis. The linkage between the validated target genes and diseases suggested that we pay particular attention to exosome miRNAs from mastitic milk in milk safety.
2022-08-31 | GSE201588 | GEO