A5033097567- Immune Response and Inflammation
- Fungal Infections and Studies
- Immune Cell Function and Interaction
- Antifungal resistance and susceptibility
- T-cell and B-cell Immunology
- IL-33, ST2, and ILC Pathways
- Antimicrobial Peptides and Activities
- interferon and immune responses
- Nail Diseases and Treatments
- Asthma and respiratory diseases
- Pediatric health and respiratory diseases
- NF-κB Signaling Pathways
- Chemokine receptors and signaling
- Respiratory Support and Mechanisms
- Neonatal Respiratory Health Research
- Inflammasome and immune disorders
- Cytokine Signaling Pathways and Interactions
- Exercise and Physiological Responses
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cancer Research and Treatments
- Heme Oxygenase-1 and Carbon Monoxide
- Systemic Lupus Erythematosus Research
- Herpesvirus Infections and Treatments
- Eosinophilic Esophagitis
- Respiratory viral infections research
McGill University Health Centre
2013-2024
McGill University
2009-2021
Christie (Canada)
2010-2021
Christ University
2014
Montreal General Hospital
1995-2013
Sanskriti Samvardhan Mandal
2011
GlaxoSmithKline (United Kingdom)
2009
University of Toronto
1995-2009
Yale University
2003
Millennium Engineering and Integration (United States)
1999
Bacterial lipopolysaccharide (LPS) provokes a vigorous, generalized proinflammatory state in the infected host. Genetic regulation of this response has been localized to Lps locus on mouse chromosome 4, through study C3H/HeJ and C57BL/10ScCr inbred strains. Both mice are homozygous for mutant allele (Lpsd/d) that confers hyporesponsiveness LPS challenge, therefore exhibit natural tolerance its lethal effects. physical mapping 1,345 backcross progeny segregating phenotype confined 0.9-cM...
The RIG-I like receptor pathway is stimulated during RNA virus infection by interaction between cytosolic and viral structures that contain short hairpin dsRNA 5′ triphosphate (5′ppp) terminal structure. In the present study, an agonist of was synthesized in vitro shown to stimulate RIG-I-dependent antiviral responses at concentrations picomolar range. human lung epithelial A549 cells, 5′pppRNA specifically multiple parameters innate response, including IRF3, IRF7 STAT1 activation, induction...
A point mutation in the Tlr4 gene, which encodes Toll-like receptor 4, has recently been proposed to underlie LPS hyporesponsiveness C3H/HeJ mice (Lpsd). The data presented herein demonstrate that F1 progeny from crosses between carry a approximately 9-cM deletion of chromosome 4 (including LpsTlr4) and (i.e., Lps0 x Lpsd mice) exhibit pattern sensitivity, measured by TNF activity, is indistinguishable exhibited Lpsn whose average response "intermediate" parental responses. Thus, these...
Abstract TLRs have been studied extensively in pathogen-mediated host responses. We use a murine model of lethal oxidant-mediated injury to demonstrate for the first time that mammalian TLR4 is required survival and lung integrity. Administering high levels inspired oxygen, or hyperoxia, commonly used as life-sustaining measure critically ill patients. However, prolonged exposures can lead respiratory failure death. TLR4-deficient mice exhibited increased mortality during hyperoxia. The...
By virtue of its direct contact with the environment, lung is constantly challenged by infectious and non-infectious stimuli that necessitate a robust yet highly controlled host response coordinated innate adaptive arms immune system. Mammalian Toll-like receptors (TLRs) function as crucial sentinels microbial antigens throughout respiratory tract mediate immunity. Selective induction inflammatory responses to harmful environmental exposures tolerance innocuous are required maintain tissue...
Acute lung injury during bacterial infection is associated with neutrophilic inflammation, epithelial cell apoptosis, and disruption of the alveolar-capillary barrier. TLR4 required for in animals exposed to LPS initiates proinflammatory responses part via transcription factor NF-κB. Ligation also a proapoptotic response by activating IFN-β STAT1-dependent genes. We recently demonstrated that mammalian target rapamycin (mTOR), key controller growth survival, can physically interact STAT1...
Toll-like receptor 4 (TLR4) recognizes specific structural motifs associated with microbial pathogens and also responds to certain endogenous host molecules tissue damage. In Duchenne muscular dystrophy (DMD), inflammation plays an important role in determining the ultimate fate of dystrophic muscle fibers. this study, we used TLR4-deficient mdx mice assess TLR4 pathogenesis DMD. expression was increased showed enhanced activation following agonist stimulation diaphragm muscle. Genetic...
Participation of B cells in the immune response by various antibody-independent mechanisms has recently been uncovered. producing cytokines have described for several infections and appear to regulate adaptive response. cell activation Leishmania donovani results disease exacerbation. How activates is still unknown. We show that L. amastigotes activate triggering endosomal TLRs; this leads induction cytokines. Cytokine expression completely abrogated from Ifnar−/− mice upon exposure...
SummaryCD4+Foxp3+ regulatory T (TREG) cells are critical mediators of peripheral tolerance and modulators immune responses. Functional adaptation TREG cells, through acquisition secondary transcription factors is for their effector differentiation towards local inflammatory stimuli including infections. The drivers consequences this cell function remain largely unknown. Using an unbiased screen, we identified receptors the IL-1 family controlling cells. Through respiratory infection models,...
Immunologically active molecules such as cytokines and chemokines have been implicated in skeletal muscle weakness during sepsis well recovery from injury. In sepsis, Toll-like receptors (TLRs) act key sentinel of the innate immune system. Here we determined cell responses two prototypical CC CXC chemokine genes (monocyte chemoattractant protein 1 [MCP-1] KC, respectively), to stimulation with specific TLR ligands. addition, examined whether NF-kappaB calcineurin signaling are involved these...
During the latter half of twentieth century, fungal pathogens such as Cryptococcus neoformans were increasingly recognized a significant threat to health immune compromised populations throughout world. Until recently, closely related species C. gattii was considered be low-level endemic pathogen that confined tropical regions Australia. Since 1999, has emerged in Pacific Northwest region North America and been responsible for large disease epidemic among generally healthy individuals. The...
A hydatidiform mole (HM) is a human pregnancy with hyperproliferative placenta and abnormal embryonic development. Mutations in NLRP7, member of the nucleotide oligomerization domain-like receptor family proteins roles inflammation apoptosis, are responsible for recurrent HMs. However, little known about functional role NLRP7. Here, we demonstrate that peripheral blood mononuclear cells from patients NLRP7 mutations rare variants secrete low levels IL-1β TNF response to LPS. We show...
Susceptibility to progressive infection with the fungus Cryptococcus neoformans is associated an allergic pattern of lung inflammation, yet factors that govern this host response are not clearly understood. Using a clinically relevant mouse model inhalational virulent C. H99, we demonstrate role for IL-33-dependent signaling in immune defense. Infection BALB/c mice 10(4) CFU H99 caused time-dependent induction IL-33 accumulation type 2 pulmonary innate lymphoid cells and alternatively...
The Th2 cytokine IL-13 regulates several aspects of the asthmatic phenotype, including airway inflammation, hyperresponsiveness, and mucus production. Th17 IL-17A is also implicated in asthma has been shown to both positively negatively regulate Th2-dependent responses murine models allergic airways disease. Our objective this study was better understand role IL-17 inflammation by examining how modifies IL-13-induced inflammatory responses. We treated BALB/c mice intranasally with or alone...
The type I interferon pathway plays a critical role in both host defense and tolerance against viral infection thus requires refined regulatory mechanisms. RIPK3-mediated necroptosis has been shown to be involved anti-viral immunity. However, the exact of RIPK3 immunity Influenza A Virus (IAV) is poorly understood. In line with others, we, herein, show that Ripk3-/- mice are highly susceptible IAV infection, exhibiting elevated pulmonary load heightened morbidity mortality. Unexpectedly,...
Surgery is required for the curative treatment of lung cancer but associated with high rates postoperative pneumonias predominantly caused by gram negative bacteria. Recent evidence suggests that these severe infectious complications may decrease long term survival after hospital discharge via recurrence, mechanism unclear. Lung cells have recently been demonstrated to express Toll‐like receptors (TLR) mediate pathogen recognition. We hypothesized incubation non‐small cell (NSCLC)...
Genetically regulated mechanisms of host defense against Cryptococcus neoformans infection are not well understood. In this study, pulmonary with the moderately virulent C. strain 24067 was used to compare resistance phenotype C57BL/6J that inbred mouse SJL/J. At 7 days or later after infection, mice exhibited a significantly greater fungal burden in lungs than SJL/J mice. Characterization innate immune response at 3 h cryptococcal revealed resistant higher neutrophilia, elevated levels...
Angiopoietins are ligands for Tie-2 receptors and play important roles in angiogenesis inflammation. While angiopoietin-1 (Ang-1) inhibits inflammatory responses, angiopoietin-2 (Ang-2) promotes cytokine production vascular leakage. In this study, we evaluated vivo vitro effects of Escherichia coli lipopolysaccharides (LPS) on angiopoietin expression. Wild-type C57/BL6 mice were injected with saline (control) or E. LPS (20 mg/ml ip) killed 6, 12, 24 h later. The diaphragm, lung, liver...
Type 1 diabetes (T1D) occurs through a breakdown of self-tolerance resulting in the autoimmune destruction insulin producing β-islets pancreas. A numerical and functional waning CD4+ Foxp3+ regulatory T (Treg) cells, prompted by pancreatic IL-2 deficiency, accompanies Th1 autoimmunity T1D progression non-obese diabetic (NOD) mice. Recently, we identified dominant subset intra-islet Treg cells that expresses ICOS costimulatory receptor promotes delaying onset T1D. co-stimulation potently...