A5085310352- Immune Response and Inflammation
- Antimicrobial Resistance in Staphylococcus
- Bacterial biofilms and quorum sensing
- T-cell and B-cell Immunology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cytokine Signaling Pathways and Interactions
- Dermatology and Skin Diseases
- Antimicrobial Peptides and Activities
- Biochemical and Structural Characterization
- Asthma and respiratory diseases
- IL-33, ST2, and ILC Pathways
- Clostridium difficile and Clostridium perfringens research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Pneumonia and Respiratory Infections
- Cell Adhesion Molecules Research
- Bacterial Infections and Vaccines
- Immune responses and vaccinations
- Immune cells in cancer
- NF-κB Signaling Pathways
- Bacterial Genetics and Biotechnology
- Microscopic Colitis
- Chemokine receptors and signaling
- Dialysis and Renal Disease Management
- COVID-19 Clinical Research Studies
Trinity College Dublin
2016-2025
Tallaght University Hospital
2004-2023
Cheshire West and Chester
2020
National Health Service
2020
RELX Group (United States)
2019
Cardiff University
2002-2014
Brigham and Women's Hospital
2006-2011
Harvard University
2006-2011
University of Wales
1999-2005
Ludwig Cancer Research
2005
Abstract The successful resolution of inflammation is dependent upon the coordinated transition from initial recruitment neutrophils to a more sustained population mononuclear cells. IL-6, which signals via common receptor subunit gp130, represents crucial checkpoint regulator neutrophil trafficking during inflammatory response by orchestrating chemokine production and leukocyte apoptosis. However, relative contribution specific IL-6-dependent signaling pathways these processes remains...
Pneumolysin (PLY) is a key Streptococcus pneumoniae virulence factor and potential candidate for inclusion in pneumococcal subunit vaccines. Dendritic cells (DC) play role the initiation instruction of adaptive immunity, but effects PLY on DC have not been widely investigated. Endotoxin-free enhanced costimulatory molecule expression did induce cytokine secretion. These functional significance as adoptive transfer exposed to antigen resulted stronger antigen-specific T cell proliferation...
Highlights•Repeated acute resolving inflammation leads to excessive tissue damage•IL-6 regulates profibrotic IFN-γ-secreting T cells•IFN-γ increases detrimental STAT1 signaling in stromal tissue•STAT1 activity alters homeostatic control of extracellular matrix promote fibrosisSummaryFibrosis response damage or persistent is a pathological hallmark many chronic degenerative diseases. By using model peritoneal inflammation, we have examined how repeated inflammatory activation promotes...
Whooping cough caused by Bordetella pertussis is a re-emerging infectious disease despite the introduction of safer acellular vaccines (Pa). One explanation for this that Pa are less protective than more reactogenic whole cell (Pw) they replaced. Although induce potent antibody responses, and protection has been found to be associated with high concentrations circulating IgG against vaccine antigens, it not firmly established host induced mediated solely humoral immunity. The aim study was...
Interleukin (IL)-6 signaling through its soluble receptor (IL-6 transsignaling) directs transition between innate and acquired immune responses by orchestrating the chemokine-directed attraction apoptotic clearance of leukocytes. Through analysis mononuclear cell infiltration in WT IL-6-deficient mice during peritoneal inflammation, we now report that IL-6 selectively governs T regulating chemokine secretion (CXCL10, CCL4, CCL5, CCL11, CCL17) (CCR3, CCR4, CCR5, CXCR3) expression on CD3 +...
Regulated recruitment and clearance of neutrophils (PMN) is the hallmark competent host defense resolution inflammation. We now report that IFN-γ controls PMN infiltration modulates IL-6 signaling through its soluble receptor (sIL-6R) to promote their apoptosis clearance. Induction peritoneal inflammation in IFN-γ–deficient (IFN-γ–/–) mice emphasized initial rate was impaired. This defect also associated with suppressed intraperitoneal expression IL-1β IL-6. Reconstitution restored levels...
Commensalism is critical to a healthy Th1/Th2 cell balance. Polysaccharide A (PSA), which produced by the intestinal commensal Bacteroides fragilis, activates CD4+ T cells, resulting in Th1 response correcting Th2 skew of germ-free mice. We identify Toll-like receptors as crucial convergence innate and adaptive responses stimulated PSA. Optimization cytokine interferon-γ PSA-stimulated dendritic cell–CD4+ co-cultures depends on both receptor (TLR) 2 antigen presentation. Synergy between was...
IL-6 responses are classically orchestrated via a membrane-bound IL-6R (CD126) alpha subunit (classical signaling) or through soluble form of this cognate receptor (IL-6 trans signaling). Appraisal expression on human and mouse T cells emphasized that is closely linked with CCR7 CD62L. In regard, infiltrating effector from clinical experimental peritonitis episodes lose expression, anti-CD3/CD28 Ab costimulation peripheral in vitro leads to downregulation expression. Consequently, signaling...
Staphylococcus aureus asymptomatically colonises the anterior nares, but host and bacterial factors that facilitate colonisation remain incompletely understood. The S. surface protein ClfB has been shown to mediate adherence squamous epithelial cells in vitro promote nasal both mice humans. Here, we demonstrate cell envelope loricrin represents major target ligand for during colonisation. In assays indicated bacteria expressing bound most likely by “dock, lock latch” mechanism. Using plasmon...
Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance cellular has been shown mice, T cell responses have not characterised. Using a murine model recurrent S. peritonitis, we demonstrated that prior exposure enhanced IFNγ upon subsequent infection, while adoptive transfer antigen-specific Th1 cells was naïve mice. Translating these findings, found were also significantly expanded during human bloodstream (BSI). These CD45RO+,...
The development of vaccines against Staphylococcus aureus has consistently failed in clinical trials, likely due to inefficient induction cellular immunity. T cell-derived IL-17 is one the few known correlates antistaphylococcoal immunity, conferring protection S. infections through its ability promote phagocytic cell effector functions. A comprehensive understanding discrete subsets critical for site-specific IL-17-mediated bacterial clearance will therefore be necessary inform that...
Detection of microbes by TLRs on the plasma membrane leads to induction proinflammatory cytokines such as TNF-α, via activation NF-κB. Alternatively, endosomal type I IFNs IFN regulatory factors (IRFs). TLR4 signaling from NF-κB Toll/IL-1R (TIR) adaptor protein MyD88 requires TIR sorting Mal, whereas IRF3 domain-containing adaptor-inducing IFN-β (TRIF) TRIF-related molecule (TRAM). Similar homodimers, TLR2 heterodimers can also induce both and IFNs. is known require IRF MyD88. However, it...
Excessive inflammation-associated coagulation is a feature of infectious diseases, occurring in such conditions as bacterial sepsis and COVID-19. It can lead to disseminated intravascular coagulation, one the leading causes mortality worldwide. Recently, type I interferon (IFN) signaling has been shown be required for tissue factor (TF; gene name F3) release from macrophages, critical initiator providing an important mechanistic link between innate immunity coagulation. The mechanism...
Abstract Interleukin-6 signaling via its soluble receptor (sIL-6R) differentially regulates inflammatory chemokine expression and leukocyte apoptosis to coordinate transition from neutrophil mononuclear cell infiltration. sIL-6R activities may, however, be influenced in vivo by the occurrence of two isoforms that are released as a consequence differential mRNA splicing (DS) or proteolytic cleavage (PC) cognate IL-6R (termed DS- PC-sIL-6R). Using human peritoneal mesothelial cells murine...
Abstract Immunomodulatory therapy represents an attractive approach in treating multidrug-resistant infections. Developing this necessitates a lucid understanding of host defense mechanisms. Neutrophils represent the first line systemic during Staphylococcus aureus However, recent research suggests that survival S. inside neutrophils may actually contribute to pathogenesis, indicating neutrophil trafficking infection site must be tightly regulated ensure efficient microbial clearance. We...
ABSTRACT The capacity for intracellular survival within phagocytes is likely a critical factor facilitating the dissemination of Staphylococcus aureus in host. To date, majority work on S. -phagocyte interactions has focused neutrophils and, to lesser extent, macrophages, yet we understand little about role played by dendritic cells (DCs) direct killing this bacterium. Using bone marrow-derived DCs (BMDCs), demonstrate first time that can effectively kill but certain strains have evade DC...
Abstract IL-10 is a potent anti-inflammatory mediator that plays crucial role in limiting host immunopathology during bacterial infections by controlling effector T cell activation. Staphylococcus aureus has previously been shown to manipulate the response as mechanism of immune evasion chronic systemic and biofilm models infection. In present study, we demonstrate divergent roles for depending on site During acute S. infection, an important protective required prevent dissemination...