Similar Datasets
Project description:Localized inflammation mediators in a murine acute mastitis model
| PRJNA737627 | ENA
Project description:Macrophages are involved in immune defense, organogenesis and tissue homeostasis. They also contribute to the different phases of mammary gland remodeling during development, pregnancy and involution post-lactation. Yet, less is known about the dynamics of mammary gland macrophages in the lactation stage. Here, we describe a macrophage population present during lactation in mice. By multi-parameter flow cytometry and single-cell RNA sequencing we reveal this population as distinct from the two resident macrophage subsets present pregestationally. These lactation-induced macrophages (LiMacs) are predominantly monocyte-derived and expand by proliferation in situ concomitant with nursing. LiMacs develop independently of IL-34 but require CSF-1 signaling and are partly microbiota-dependent. Locally, they reside adjacent to the basal cells of the alveoli and extravasate into the milk. Moreover, we also found several macrophage subsets in human milk, resembling LiMacs. Collectively, these findings reveal the emergence of unique macrophages in the mammary gland and milk during lactation.
2023-06-23 | PXD041711 | Pride
Project description:We performed a genome-wide transcriptional analysis in the mammary gland in a mouse model of E. coli mastitis using high-density mouse oligonucleotide microarrays. This global transcription analysis revealed that about 7% of tested genes are mobilized in the mouse mammary gland to E. coli endotoxin. We identified 1402 differentially expressed genes that were associated with physiological system development/function and molecular/cellular functions and metabolic/signalling pathways that are highly relevant to host immune-inflammatory defense response against E. coli infection. The mouse differentially expressed genes through the use of comparative mapping/genomics and positional information on reported QTL for bovine mastitis allowed identifying 293 potential candidate genes for bovine mastitis. This study will enable other researchers to combine our mRNA expression data with genetic association studies to discover genomic variation underlying variation of susceptibility to mastitis in dairy cows. Keywords: time course, disease state analysis This study was conducted using a split-plot design. We measured levels of gene expression in healthy (saline injected) and diseased (E. coli injected) mammary gland tissue (treatment = 2, in sub-plots). The mammary tissue samples were collected at two-time points: 24 hr and 48 hr post-injection (time = 2, in main-plots). Each inbred mouse was injected with both treatments: the 4th left mammary gland was injected with saline solution and the 4th right mammary gland was injected with E. coli solution (mice = 4). The expression profiling was carried out using two biological replications (replication = 2) at each time point.
2011-06-29 | E-GEOD-14485 | biostudies-arrayexpress
Project description:Mastitis is one of the most prevalent and economically important diseases of dairy animals. The disease is caused by ascending bacterial infection through the teat canal. Among the most common mastitis-causing bacteria are gram-negative coliforms, gram-positive streptococci and staphylococci, and mycoplasma. The most prominent cellular hallmark of acute mammary infection is a massive recruitment of blood neutrophils into the tubular and alveolar milk spaces. The complex biological processes of leukocyte recruitment, activation, adhesion, and migration in the mammary gland remain largely elusive to date. While field research of mastitis in dairy animals contributed a lot to the development of mitigation, control, and even eradication programs, little progress was made toward understanding the molecular mechanisms underlying the pathogenesis of the disease. We report here experimental mastitis model systems in lactating mice challenged with field strains of common udder pathogens in dairy cows. We used these model systems to apply recently developed multiplex gene expression technology (Nanostring nCounter), which enabled us to study the expression of over 700 immune genes. Our analysis revealed a core of 100 genes that are similarly regulated and functionally or physically interacting in E. coli, M. bovis and Strep uberis murine mastitis. Common significantly enriched gene sets include TNFɑ signaling via NFkB, Interferon gamma and alpha response, and IL6-JAK-STAT3 signaling. In addition, we show a significantly enriched expression of genes associated with neutrophil extracellular traps (NET) in glands challenged by the three pathogens. Ligand-receptor analysis revealed interactions shared by the three pathogens, including the interaction of the cytokines IL1β, IL1ɑ, and TNFɑ with their receptors, and proteins involved in immune cell recruitment such as complement C3 and ICAM1 (with CD11b), chemokines CCL3 and CCL4 (with CCR1), and CSF3 (with CSF3R). Taken together, our results show that mammary infection with E. coli, M. bovis and Strep uberis culminated in the activation of a conserved core of immune genes and pathways including NET formation.
2023-04-12 | GSE225127 | GEO
Project description:Macrophages are involved in immune defense, organogenesis and tissue homeostasis. They also contribute to the different phases of mammary gland remodeling during development, pregnancy and involution post-lactation. Yet, less is known about the dynamics of mammary gland macrophages in the lactation stage. Here, we describe a macrophage population present during lactation in mice. By multi-parameter flow cytometry and single-cell RNA sequencing we reveal this population as distinct from the two resident macrophage subsets present pregestationally. These lactation-induced macrophages (LiMacs) are predominantly monocyte-derived and expand by proliferation in situ concomitant with nursing. LiMacs develop independently of IL-34 but require CSF-1 signaling and are partly microbiota-dependent. Locally, they reside adjacent to the basal cells of the alveoli and extravasate into the milk. Moreover, we also found several macrophage subsets in human milk, resembling LiMacs. Collectively, these findings reveal the emergence of unique macrophages in the mammary gland and milk during lactation.
2023-05-03 | GSE230749 | GEO
Project description:Macrophages are involved in immune defense, organogenesis and tissue homeostasis. They also contribute to the different phases of mammary gland remodeling during development, pregnancy and involution post-lactation. Yet, less is known about the dynamics of mammary gland macrophages in the lactation stage. Here, we describe a macrophage population present during lactation in mice. By multi-parameter flow cytometry and single-cell RNA sequencing we reveal this population as distinct from the two resident macrophage subsets present pregestationally. These lactation-induced macrophages (LiMacs) are predominantly monocyte-derived and expand by proliferation in situ concomitant with nursing. LiMacs develop independently of IL-34 but require CSF-1 signaling and are partly microbiota-dependent. Locally, they reside adjacent to the basal cells of the alveoli and extravasate into the milk. Moreover, we also found several macrophage subsets in human milk, resembling LiMacs. Collectively, these findings reveal the emergence of unique macrophages in the mammary gland and milk during lactation.
2023-05-03 | GSE230697 | GEO
Project description:We performed a genome-wide transcriptional analysis in the mammary gland in a mouse model of E. coli mastitis using high-density mouse oligonucleotide microarrays. This global transcription analysis revealed that about 7% of tested genes are mobilized in the mouse mammary gland to E. coli endotoxin. We identified 1402 differentially expressed genes that were associated with physiological system development/function and molecular/cellular functions and metabolic/signalling pathways that are highly relevant to host immune-inflammatory defense response against E. coli infection. The mouse differentially expressed genes through the use of comparative mapping/genomics and positional information on reported QTL for bovine mastitis allowed identifying 293 potential candidate genes for bovine mastitis. This study will enable other researchers to combine our mRNA expression data with genetic association studies to discover genomic variation underlying variation of susceptibility to mastitis in dairy cows. Keywords: time course, disease state analysis
2011-06-30 | GSE14485 | GEO
Project description:The study investigated the acute and simultaneous response of the mammary and liver transcriptome to an intra-mammary lipopolysaccharide (LPS) challenge in early-lactating cows, and its consequences on metabolic biomarkers and liver composition. At 7 days of lactation, 7 cows served as controls (CTR) and 7 cows (LPS) received an intra-mammary E. coli LPS challenge. The mammary and liver tissues were sampled at 2.5 h from challenge for transcriptomic profiling. Liver composition was evaluated at 2.5 h and 7 d after challenge and blood biomarkers were analized at -2, 3, 7 and 14 d from challenge. In mammary tissue, the LPS challenge resulted in 189 differentially expressed gene (DEG), with 20 downregulated and 169 upregulated, while in the liver were found 107 DEG with 42 downregulated and 65 upregulated in LPS vs CTR. In the udder, the Dynamic Impact Approach (DIA) highlighted the activation of NOD-like receptor signaling, Toll-like receptor signaling, RIG-I-like receptor signaling and Apoptosis pathways, while in the liver were inhibited the Fatty acid elongation in mitochondria and activated the p53 signaling pathway. The LPS induced the alteration of liver lipid metabolism (rise of total lipid and triglyceride concentration), a systemic inflammation (rise of blood ceruloplasmin and bilirubin) and an increase of body fat mobilization. In cows subjected to intra-mammary LPS, the mammary gland responds activating mechanisms of pathogen recognition. In the liver the response likely depends by mediators coming from udder and affects the liver functionality and mainly the fatty acid metabolism.
2014-12-17 | GSE64225 | GEO
Project description:Mastitis remains one of the most prevalent and costly diseases impacting the dairy industry worldwide. Escherichia coli is an environmental bacterium that frequently causes intramammary infections, the outcome of which depends on the capacity of the host to recognize and clear the bacterial pathogen. E. coli intramammary infection elicits localized and systemic responses, some of which have been characterized in mammary secretory tissue. However, nothing is known about early transcriptome-wide responses to infection that occur within regions of the teat and mammary parenchyma. Therefore, the objective of the current study was to use microarray analysis to characterize gene expression patterns and process networks that become activated in different regions of the mammary gland during the acute phase of experimentally induced intramammary infection with E. coli. Tissues evaluated were from Furstenberg’s rosette, teat cistern, gland cistern, and lobulo-alveolar regions of control and infected mammary glands, 12 and 24 h after bacterial (or control) infusions. For selected genes, quantitative RT-PCR was performed to confirm the microarray findings (Toll-like receptors; TLR1, TLR2, TLR4, TLR6) and evaluate the correspondence between mRNA level in tissues and protein level in milk (interleukin 8, tumor necrosis factor-alpha, haptoglobin, lipopolysaccharide-binding protein). The main networks activated by E. coli infection pertained to immune and inflammatory response, with marked induction of genes encoding proteins that function in chemotaxis, leukocyte activation and signaling. Genomic response was greatest in tissues of the teat and gland cisterns at 12 h post-infection, while tissue of the lobulo-alveolar region responded only, and most strongly of the regions, 24 h following the infection. Up regulation of TLR2, TLR4, IL8, TNF-alpha and bactericidal/permeability-increasing protein peaked at 12 h post infection in tissues of the teat and in the gland cistern, while the highest level of lipopolysaccharide-binding protein was reached at 24 h in the lobular alveoli region of infected quarters. Very few genes were down–regulated within the timeframe of this study. Similar genetic networks were impacted in all regions during early phases of E. coli intramammary infection, although regional differences throughout the gland were noted. Importantly, the tissues of the teat, which are first to encounter invading bacteria during a natural infection, responded rapidly and intensely, suggesting an important sentinel function for this region. Both resident mammary cells and infiltrating immune cells likely play an important role in recognition of pathogens and production of inflammatory mediators during mastitis. Three healthy lactating Holstein cows were used in this study. All mammary glands were bacteria-free. Immediately following the morning milking, 4 mL of E. coli suspension (100 colony forming units/mL) were infused into one mammary gland of the udder and the contralateral gland was infused with PBS (control gland). After the PM milking 12 h later, the remaining ipsilateral quarter was infused with E. coli. Cows were euthanized 24 h after initial infusions and tissues were collected from 4 regions of each mammary gland: Furstenburg’s rosette, teat cistern, gland cistern and lobuloalveolar regions. Tissues were snap frozen in liquid nitrogen, stored at -80C until processing.
2009-08-18 | E-GEOD-15441 | biostudies-arrayexpress
Project description:Clinical studies have linked use of progestins (synthetic progesterone (P4)) to breast cancer risk. However, little is understood regarding the role native P4, signaling through the progesterone receptor (PR), plays in formation of breast tumors. Studies published by our lab highlighted a link between PR and immune signaling pathways, suggesting PR induces PR to repress the interferon signaling pathway. Given these findings, we sought to investigate whether P4/PR drive immunomodulation in the mammary gland and development of mammary gland tumors. We found that mice treated with P4 displayed changes in the mammary gland suggesting inhibited immune response compared to placebo-treated mice. Furthermore, transgenic mice with PR overexpression demonstrated decreased numbers of immune cell populations in their mammary gland, lymph nodes, and spleens. Upon long-term monitoring, we determined that multi-parous PR overexpressing mice developed significantly more mammary gland tumors than control mice. Additionally, tumors of PR overexpressing mice contained fewer infiltrating immune cells. Finally, RNA sequencing analysis of tumor samples revealed that immune-related gene signatures were enriched in tumors of control mice compared to tumors of PR overexpressing mice. Together, these findings provide a novel mechanism behind P4-mediated promotion of mammary gland tumor development and provide rationale to investigate anti-progestin treatment to promote immune-mediated elimination of mammary gland tumors.
2021-09-15 | GSE158134 | GEO