A5027867579- Immune cells in cancer
- Parasites and Host Interactions
- IL-33, ST2, and ILC Pathways
- Parasitic Diseases Research and Treatment
- MicroRNA in disease regulation
- Immune Cell Function and Interaction
- Cytokine Signaling Pathways and Interactions
- Cardiac Fibrosis and Remodeling
- Invertebrate Immune Response Mechanisms
- Asthma and respiratory diseases
- Parasitic infections in humans and animals
- Parasitic Infections and Diagnostics
- Helminth infection and control
- Immunodeficiency and Autoimmune Disorders
- Immune Response and Inflammation
- Signaling Pathways in Disease
- interferon and immune responses
- Immunotherapy and Immune Responses
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Studies on Chitinases and Chitosanases
- Eosinophilic Disorders and Syndromes
- Phagocytosis and Immune Regulation
- Hernia repair and management
- T-cell and B-cell Immunology
- Endometriosis Research and Treatment
University of Manchester
2016-2023
Manchester Academic Health Science Centre
2017-2023
University of Edinburgh
2011-2018
Centre for Immunity, Infection and Evolution
2011-2018
Wellcome Centre for Cell-Matrix Research
2017-2018
Research Center Borstel - Leibniz Lung Center
2006-2017
Medical Research Council
2013
Roslin Institute
2013
Centre for Inflammation Research
2013
Institute of Immunology
2013
A defining feature of inflammation is the accumulation innate immune cells in tissue that are thought to be recruited from blood. We reveal a distinct process exists which macrophages undergo rapid situ proliferation order increase population density. This inflammatory mechanism occurred during T helper 2 (T(H)2)-related pathologies under control archetypal T(H)2 cytokine interleukin-4 (IL-4) and was fundamental component because exogenous IL-4 sufficient drive through self-renewal. Thus,...
Macrophages (MΦs) colonize tissues during inflammation in two distinct ways: recruitment of monocyte precursors and proliferation resident cells. We recently revealed a major role for IL-4 the proliferative expansion MΦs Th2-biased tissue nematode infection. now show that intestinal as well infection is restricted to sites production requires MΦ-intrinsic IL-4R signaling. However, both IL-4Rα–dependent –independent mechanisms contributed MΦ infections. IL-4R–independent was controlled by...
The molecular basis of signal-dependent transcriptional activation has been extensively studied in macrophage polarization, but our understanding remains limited regarding the determinants repression. Here we show that IL-4-activated STAT6 transcription factor is required for direct repression a large number genes during vitro and vivo alternative polarization. Repression results decreased lineage-determining factor, p300, RNA polymerase II binding followed by reduced enhancer expression,...
Immunity to many human and murine gastrointestinal helminth parasites requires interleukin-4 (IL-4)-directed type 2 helper (T
Abstract IL-12 is a potent inducer of IFN-γ production and promotes protective cell-mediated immune response after Mycobacterium tuberculosis infection. Recently, the IL-12-related cytokine IL-27 was discovered, WSX-1 identified as one component IL-27R complex. To determine functional significance IL-27/WSX-1 during tuberculosis, we analyzed course infection in WSX-1-KO mice aerosol with M. tuberculosis. In absence WSX-1, an increased proinflammatory cytokines TNF IL-12p40 resulted elevated...
ABSTRACT Macrophages become activated by their environment and develop polarized functions: classically (M1) macrophages eliminate pathogens but can cause tissue injury, whereas alternatively (M2) promote healing repair. Mechanisms directing activation, especially in vivo, are not understood completely, here, we examined the role of SOCS proteins. M2 vitro or elicited implanting mice i.p. with parasitic nematode Brugia malayi display a selective IL-4-dependent up-regulation SOCS1 SOCS3....
BackgroundCells undergoing apoptosis are known to modulate their tissue microenvironments. By acting on phagocytes, notably macrophages, apoptotic cells inhibit immunological and inflammatory responses promote trophic signaling pathways. Paradoxically, because of potential cause death tumor thereby militate against malignant disease progression, both tumor-associated macrophages (TAMs) often associated with poor prognosis in cancer. We hypothesized that, progression disease, constitutive...
The recent revolution in tissue-resident macrophage biology has resulted largely from murine studies performed C57BL/6 mice. Here, using both and BALB/c mice, we analyze immune cells the pleural cavity. Unlike naive large-cavity macrophages (LCMs) of mice failed to fully implement tissue-residency program. Following infection with a pleural-dwelling nematode, these pre-existing differences were accentuated LCM expansion occurring C57BL/6, but not While drove monocyte recruitment strains,...
Ym1 and RELMα are established effector molecules closely synonymous with Th2-type inflammation associated pathology. Here, we show that whilst largely dependent on IL-4Rα signaling during a type 2 response, also have IL-4Rα-independent expression patterns in the lung. Notably, found has opposing effects immunity nematode infection depending whether it is expressed at time of innate or adaptive responses. During lung migratory stage Nippostrongylus brasiliensis, promoted subsequent reparative...
In ST-segment elevation myocardial infarction of both patients and mice, there was a decline in blood eosinophil count, with activated eosinophils recruited to the infarct zone. Eosinophil deficiency resulted attenuated anti-inflammatory macrophage polarization, enhanced inflammation, increased scar size, deterioration structure function. Adverse cardiac remodeling setting prevented by interleukin-4 therapy.
Tissue resident macrophages have vital homeostatic roles in many tissues but their are less well defined the heart. The present study aimed to identify density, polarisation status and distribution of healthy murine heart investigate ability respond immune challenge. Histological analysis hearts from CSF-1 receptor (csf1-GFP; MacGreen) CX3CR1 (Cx3cr1(GFP/+)) reporter mice revealed a sparse population GFP positive that were evenly distributed throughout left right ventricular free walls...
Immunity to intestinal helminth infections requires the rapid activation of T helper 2 cells (Th2 cells). However, simultaneous expansion CD4+Foxp3+ regulatory (T reg cells) impedes protective responses, resulting in chronic infections. The ratio between and effector can therefore determine outcome infection. redifferentiation into Th has been identified hyperinflammatory diseases. In this study, we asked whether ex–T Th2 develop contribute type-2 immunity. Using multigene reporter...
Both TH2-dependent helminth killing and suppression of the TH2 effector response have been attributed to macrophages (MΦ) activated by IL-4 (M(IL-4)). To investigate how M(IL-4) contribute diverse infection outcomes, MΦ compartment susceptible BALB/c mice more resistant C57BL/6 was profiled during pleural cavity with filarial nematode, Litomosoides sigmodontis. exhibited a profoundly expanded resident (resMΦ) population, which gradually replenished from bone marrow in an age-dependent...
ABSTRACT The larval stage of the cestode parasite Echinococcus granulosus causes hydatid disease in humans and livestock. This infection is characterized by growth internal organ parenchymae fluid-filled structures (hydatids) that elicit surprisingly little inflammation spite their massive size persistence. Hydatids are protected a millimeter-thick layer mucin-based extracellular matrix, termed laminated (LL), which thought to be major factor determining host response infection. Host cells...
Rapid reprogramming of the macrophage activation phenotype is considered important in defense against consecutive infection with diverse infectious agents. However, setting persistent, chronic functional importance macrophage-intrinsic adaptation to changing environments vs. recruitment new macrophages remains unclear. Here we show that resident peritoneal expanded by nematode Heligmosomoides polygyrus bakeri altered their response Salmonella enterica ser. Typhimurium vitro and vivo. The...
Abstract Inflammatory bowel disease ( IBD ) is a condition of chronic inflammatory intestinal disorder with increasing prevalence but limited effective therapies. The purine metabolic pathway involved in various processes including . However, the mechanisms through which metabolism modulates remain to be established. Here, we found that mucosal expression genes altered patients active ulcerative colitis UC ), associated elevated gene signatures group 3 innate lymphoid cell ILC 3)–interleukin...
IL-4-driven alternative macrophage activation and proliferation are characteristic features of both antihelminthic immune responses wound healing in contrast to classical activation, which primarily occurs during inflammatory responses. The signaling pathways defining the genome-wide microRNA expression profile as well cellular functions controlled by microRNAs largely unknown. Hence, current work we examined regulation function IL-4-regulated human mouse activation. We utilized...
IL‐33 plays an important role in the initiation of type‐2 immune responses, as well enhancement type 2 effector functions. Engagement receptor on macrophages facilitates polarization to alternative activation state by amplifying IL‐4 and IL‐13 signaling IL‐4Rα. also induce macrophage proliferation but involvement this process has not been rigorously evaluated. As expected, vivo delivery induced IL‐4Rα‐dependent serous cavities. proliferate but, unexpectedly, was independent IL‐4Rα signaling....