Demi Brownlie
A5027528062- Fibroblast Growth Factor Research
- Immune Cell Function and Interaction
- Cytokine Signaling Pathways and Interactions
- Immune cells in cancer
- Chemokine receptors and signaling
- COVID-19 Clinical Research Studies
- T-cell and B-cell Immunology
- SARS-CoV-2 and COVID-19 Research
- Long-Term Effects of COVID-19
- IL-33, ST2, and ILC Pathways
- Immunotherapy and Immune Responses
- Phagocytosis and Immune Regulation
- COVID-19 and Mental Health
- Epigenetics and DNA Methylation
- Immune responses and vaccinations
- Eosinophilic Esophagitis
- Reproductive System and Pregnancy
- Cytomegalovirus and herpesvirus research
- Single-cell and spatial transcriptomics
- Tryptophan and brain disorders
- Nanoplatforms for cancer theranostics
- Cancer Immunotherapy and Biomarkers
- Cancer Cells and Metastasis
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuropeptides and Animal Physiology
Karolinska University Hospital
2020-2024
Karolinska Institutet
2020-2024
Integrated Cardio Metabolic Centre
2023
MRC Centre for Reproductive Health
2018-2021
Queen's Medical Centre
2018-2021
University of Edinburgh
2018-2021
University of Glasgow
2018
Understanding innate immune responses in COVID-19 is important to decipher mechanisms of host and interpret disease pathogenesis. Natural killer (NK) cells are effector lymphocytes that respond acute viral infections but might also contribute immunopathology. Using 28-color flow cytometry, we here reveal strong NK cell activation across distinct subsets peripheral blood patients. This pattern was mirrored scRNA-seq signatures bronchoalveolar lavage from Unsupervised high-dimensional analysis...
MAIT cell activation and decline in blood are associated with COVID-19 severity, features that dynamically recover convalescence.
Dendritic cells (DCs) and monocytes are crucial mediators of innate adaptive immune responses during viral infection, but misdirected by these may contribute to immunopathology. Here, we performed high-dimensional flow cytometry-analysis focusing on mononuclear phagocyte (MNP) lineages in SARS-CoV-2-infected patients with moderate severe COVID-19. We provide a deep comprehensive map the MNP landscape A redistribution monocyte subsets toward intermediate general decrease circulating DCs was...
The functional diversity of natural killer (NK) cell repertoires stems from differentiation, homeostatic, receptor-ligand interactions and adaptive-like responses to viral infections. In the present study, we generated a single-cell transcriptional reference map healthy human blood- tissue-derived NK cells, with temporal resolution fate-specific expression gene-regulatory networks defining differentiation. Transfer learning facilitated incorporation tumor-infiltrating transcriptomes (39...
Metastasis-associated macrophages (MAMs) play pivotal roles in breast cancer metastasis by promoting extravasation and survival of metastasizing cells. In a metastatic mouse model, we previously reported that circulating classical monocytes (C-MOs) preferentially migrated into the tumor-challenged lung where they differentiated MAMs. However, fate characteristics C-MOs site has not been defined. this study, identified adoptively transferred (F4/80lowCD11b+Ly6C+) distinct myeloid cell...
Human adaptive-like "memory" CD56dimCD16+ natural killer (NK) cells in peripheral blood from cytomegalovirus-seropositive individuals have been extensively investigated recent years and are currently explored as a treatment strategy for hematological cancers. However, of solid tumors remains limited due to insufficient NK cell tumor infiltration, it is unknown whether large expansions that equipped tissue residency homing exist tissues. Here, we show human lung contains CD56brightCD16- with...
Respiratory viral infections with SARS-CoV-2 and influenza viruses commonly induce a strong infiltration of immune cells into the human lung, potential detrimental effects on integrity lung tissue. Despite comprising largest fractions circulating lymphocytes in rather little is known about how peripheral blood natural killer (NK) cell T subsets are equipped for lung-homing COVID-19 influenza. Here, we provide detailed comparative analysis NK patients infected or virus, focusing protein gene...
Lung cancer is a leading cause of cancer-related death worldwide. Despite recent advances in tissue immunology, little known about the spatial distribution tissue-resident lymphocyte subsets lung tumors. Using high-parameter flow cytometry, we identified an accumulation lymphocytes including NK (trNK) cells and CD8+ memory T (TRM) toward center human non-small cell carcinomas (NSCLC). Chemokine receptor expression patterns indicated different modes tumor-infiltration and/or residency between...
Mucosal-associated invariant T (MAIT) cells are unconventional that recognize microbial riboflavin pathway metabolites presented by evolutionarily conserved MR1 molecules. We explored the human MAIT cell compartment across organ donor–matched blood, barrier, and lymphoid tissues. population size was donor dependent with distinct tissue compartmentalization patterns adaptations: Intestinal CD103 + resident an immunoregulatory CD39 high CD27 low profile, whereas expressing NCAM1/CD56 dominated...
Chemokines have been shown to be essential players in a range of cancer contexts. In this study, we demonstrate that mice deficient the atypical chemokine receptor Ackr2 display impaired development metastasis vivo both cell line and spontaneous models. Further analysis reveals relates increased expression CCR2, specifically by KLRG1
Background Metastatic breast cancer is a leading cause of cancer-related death in women worldwide. Infusion natural killer (NK) cells an emerging immunotherapy for such malignant tumors, although elimination the immunosuppressive tumor environment required to improve its efficacy. The effects this “metastatic” on NK cells, however, remain largely unknown. Previous studies, including our own, have demonstrated that metastasis-associated macrophages (MAMs) are one most abundant immune cell...
Understanding innate immune responses in COVID-19 is important for deciphering mechanisms of host and interpreting disease pathogenesis. Natural killer (NK) cells are effector lymphocytes that respond to acute viral infections, but might also contribute pathology. Here, using 28-color flow cytometry, we describe a state strong NK cell activation across distinct subsets peripheral blood patients, pattern mirrored scRNA-seq signatures lung cells. Unsupervised high-dimensional analysis...
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to disease increased morbidity and mortality among certain risk groups. The presence of autoantibodies against type I interferons (aIFN-Abs) is one mechanism that contributes 2019 (COVID-19).
Innate lymphoid cells (ILCs) contribute to immune defense, yet it is poorly understood how ILCs develop and are strategically positioned in the lung. This applies especially human due difficulty of studying them vivo. Here we investigated ontogeny migration vivo with a humanized mouse model ("MISTRG") expressing cytokines. In addition known tissue-resident ILC subsets, discovered CD5-expressing that predominantly resided within lung vasculature circulation. CD5+ contained IFNγ-producing...
Metastasis-associated macrophages (MAM) promote persistent growth of breast cancer cells at the metastatic site and are, thus, an attractive therapeutic target to treat metastasis, a leading cause cancer-related death in women. However, precise mechanisms behind MAM-mediated tumor outgrowth have not been fully elucidated. Using mouse models cancer, we showed that MAMs uniquely expressed hepatocyte factor (HGF) tumors. We also demonstrated selected population with high potential (cancer can...
Abstract Respiratory viral infections with SARS-CoV-2 or influenza viruses commonly induce a strong infiltration of immune cells into the lung, potential detrimental effects on integrity lung tissue. Despite comprising largest fractions circulating lymphocytes in little is known about how blood natural killer (NK) and T cell subsets are equipped for lung-homing COVID-19 influenza. Using 28-colour flow cytometry re-analysis published RNA-seq datasets, we provide detailed comparative analysis...
Host genetics shape immune responses and influence severity of infectious diseases. The HLA-B -21 M/T dimorphism tunes the functionality natural killer (NK) cells expressing inhibitory receptor NKG2A. NKG2A
<div>Abstract<p>Metastasis-associated macrophages (MAM) promote persistent growth of breast cancer cells at the metastatic site and are, thus, an attractive therapeutic target to treat metastasis, a leading cause cancer-related death in women. However, precise mechanisms behind MAM-mediated tumor outgrowth have not been fully elucidated. Using mouse models cancer, we showed that MAMs uniquely expressed hepatocyte factor (HGF) tumors. We also demonstrated selected population with...
<div>Abstract<p>Metastasis-associated macrophages (MAM) promote persistent growth of breast cancer cells at the metastatic site and are, thus, an attractive therapeutic target to treat metastasis, a leading cause cancer-related death in women. However, precise mechanisms behind MAM-mediated tumor outgrowth have not been fully elucidated. Using mouse models cancer, we showed that MAMs uniquely expressed hepatocyte factor (HGF) tumors. We also demonstrated selected population with...
<p>Effects of MET signaling on susceptibility cancer cells to NK cells.</p>
<p>Detection and depletion of NK cells in mice with metastatic tumors.</p>
<p>NK cell cytotoxicity against E0771-LG cells.</p>
<p>Validation of antibodies used to detect HGF and immune cells.</p>