A5107169245- Immune Response and Inflammation
- Inflammasome and immune disorders
- IL-33, ST2, and ILC Pathways
- interferon and immune responses
- Immune Cell Function and Interaction
- Pneumonia and Respiratory Infections
- Pediatric health and respiratory diseases
- Neonatal Respiratory Health Research
- Immunotherapy and Immune Responses
- Immunodeficiency and Autoimmune Disorders
- Antimicrobial Peptides and Activities
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Asthma and respiratory diseases
- Psoriasis: Treatment and Pathogenesis
- Evaluation and Performance Assessment
- Diversity and Career in Medicine
- Congenital gastrointestinal and neural anomalies
- Child Nutrition and Water Access
- Service-Learning and Community Engagement
- Immune responses and vaccinations
- Adipokines, Inflammation, and Metabolic Diseases
- S100 Proteins and Annexins
- Intestinal Malrotation and Obstruction Disorders
- Pharmaceutical Practices and Patient Outcomes
- Hippo pathway signaling and YAP/TAZ
Trinity College Dublin
2016-2025
Tallaght University Hospital
2021-2023
National Children’s Research Centre
2022
Corporació Sanitària Parc Taulí
2018
Universidad de la República
2010-2016
Hospital Universitario de San Vicente Fundación
2011
Universidad de Antioquia
2011
University of Valparaíso
2011
ABSTRACT Streptococcus pneumoniae is a major cause of pneumonia in infants and the elderly. Innate defenses are essential to control pneumococcal infections, deficient responses can trigger disease susceptible individuals. Here we showed that flagellin locally activate innate immunity thereby increase resistance acute pneumonia. Flagellin mucosal treatment improved S. clearance lungs promoted increased survival infection. In addition, lung architecture was fully restored after infected mice,...
Increased glycolytic metabolism recently emerged as an essential process driving host defense against Mycobacterium tuberculosis (Mtb), but little is known about how this regulated during infection. Here, we observe repression of glycolysis in Mtb-infected macrophages, which dependent on sustained upregulation anti-inflammatory microRNA-21 (miR-21) by proliferating mycobacteria. The dampening miR-21 mediated through targeting phosphofructokinase muscle (PFK-M) isoform at the committed step...
The effectiveness of many vaccines licensed for clinical use relates to the induction neutralising antibodies, facilitated by inclusion vaccine adjuvants, particularly alum. However, ability alum preferentially promote humoral rather than cellular, Th1-type responses, is not well understood. We demonstrate that activates immunosuppressive mechanisms following vaccination, which limit its capacity induce Th1 responses. One key cytokines limiting excessive immune responses IL-10. Injection...
The non-canonical inflammasome sensor caspase-11 and gasdermin D (GSDMD) drive inflammation pyroptosis, a type of immunogenic cell death that favors cell-mediated immunity (CMI) in cancer, infection, autoimmunity. Here we show GSDMD are required for CD8+ Th1 responses induced by nanoparticulate vaccine adjuvants. We demonstrate nanoparticle-induced reactive oxygen species (ROS) size dependent essential CMI, identify 50- to 60-nm nanoparticles as optimal inducers ROS, activation, responses....
Summary Despite the efficacy of current immune‐chemotherapy for treatment B ‐cell non‐ H odgkin lymphoma, a substantial proportion patients relapse, highlighting need new therapeutic modalities. The use live microorganisms to develop anti‐tumoural therapies has evolved since C oley's toxin and is now receiving renewed attention. S almonella T yphimurium been shown be highly effective as an anti‐tumour agent in many solid cancer models, but it not used haemato‐oncology. Here, we report that...
Humans that are heterozygous for the common S180L polymorphism in Toll-like receptor (TLR) adaptor Mal (encoded by TIRAP) protected from a number of infectious diseases, including tuberculosis (TB), whereas those homozygous allele at increased risk. The reason this difference susceptibility is not clear. We report has TLR-independent role interferon-gamma (IFN-γ) signaling. Mal-dependent IFN-γ (IFNGR) signaling led to mitogen-activated protein kinase (MAPK) p38 phosphorylation and autophagy....
Chitosan is a cationic polysaccharide that has been evaluated as an adjuvant due to its biocompatible and biodegradable nature. The can enhance antibody responses cell-mediated immunity following vaccination by injection or mucosal routes. However, the optimal polymer characteristics for activation of dendritic cells (DCs) induction antigen-specific cellular immune have not resolved. Here, we demonstrate only chitin-derived polymers with high degree deacetylation (DDA) generation...
Prophylactic intranasal administration of the Toll-like receptor 5 (TLR5) agonist flagellin protects mice against respiratory pathogenic bacteria. We hypothesized that TLR5-mediated stimulation lung immunity might improve therapeutic index antibiotics for treatment Streptococcus pneumoniae infections in mice. Intranasal was combined with either oral amoxicillin or intraperitoneal injection trimethoprim-sulfamethoxazole to treat S. pneumoniae-infected animals. Compared standalone treatments,...
Stimulator of IFN genes (STING) is a promising target for adjuvants utilized in situ cancer vaccination approaches. However, key barriers remain clinical translation, including low cellular uptake and accessibility, STING variability necessitating personalized agonists, interferon (IFN)-independent signals that can promote tumor growth. Here, we identify C100, highly deacetylated chitin-derived polymer (HDCP), as an attractive alternative to conventional agonists. C100 promotes potent...
SUMMARY Infection by larval Echinococcus granulosus is usually characterized tight inflammatory control. However, various degrees of chronic granulomatous inflammation are also observed, reaching a high point in infection cattle the most prevalent parasite strain worldwide, which not well adapted to this host species. In context, epithelioid and multinucleated giant macrophages surround parasite, secreted products these cells often associate with wall. The phagocyte-specific S100 proteins,...
Interleukin-1 (IL-1) family cytokines are key barrier that typically expressed as inactive, or partially active, precursors require proteolysis within their amino termini for activation. IL-37 is an enigmatic member of the IL-1 has been proposed to be activated by caspase-1 and exert anti-inflammatory activity through engagement IL-18R SIGIRR. However, here we show longest isoform, IL-37b, exhibits robust proinflammatory upon amino-terminal neutrophil elastase cathepsin S. In sharp contrast,...
Aim: To evaluate efficacy of sublingual flagellin to treat acute pneumonia. Materials & methods: Mice were treated sublingually with and challenged intranasally a lethal dose pneumococcus. Flagellins lacking TLR5 or NLRC4 activation domains used assess their contribution protection. Results: Sublingual protected mice in TLR5-dependent, NLRC4-independent fashion. Neutrophils required for Flagellin-stimulated lung epithelial cells recapitulated the lung's transcriptional profile suggesting...
Signaling through Toll-like receptors (TLRs), the main in innate immunity, is essential for defense of mucosal surfaces. It was previously shown that systemic TLR5 stimulation by bacterial flagellin induces an immediate, transient interleukin-22 (IL-22)-dependent antimicrobial response to or viral infections mucosa. This process dependent on activation type 3 lymphoid cells (ILCs). The objective present study analyze effects treatment a murine model oral infection with Yersinia...
Uncoupling proteins (UCPs) are members of the mitochondrial anion carrier superfamily that can mediate transfer protons into matrix from intermembrane space. We have previously reported UCP3 expression in thymocytes, mitochondria total splenocytes and splenic lymphocytes. Here, we demonstrate Ucp3 is expressed peripheral naive CD4 + T cells at mRNA level before being markedly downregulated following activation. Non-polarized, activated (Th0 cells) -/- mice produced significantly more IL-2,...