Header Logo

Search Result Details

This page shows the details of why an item matched the keywords from your search.
One or more keywords matched the following properties of Lien, Egil
PropertyValue
overview

Research Interests:

Pathogen activation and evasion of innate immune signaling - cell death pathways, inflammasomes and Toll-like Receptors.

Over the last three decades, we have gained a lot of information on how the body defends itself against pathogenic microbes by activation of the innate immune system. This part of the immune system provides the immediate defense against invading bacteria, virus or fungi, and is also able to fine-tune and optimize the subsequent more specialized adaptive immune response.

My laboratory is primarily focused on understanding how recognition of pathogens leads to activation of Toll-like receptors (TLRs), inflammasomes, and cell death pathways. Lipopolysaccharide (LPS) from Gram-negative bacteria (also called endotoxin) is particularly interesting, it is a saccharide containing acyl chains. LPS is a main component of the Gram-negative outer membrane, and one of the most potent activators of immune cells. LPS activates cells via TLR4 and MD-2, but recognition of other microbial components, such as secretion system apparatus interacting with inflammasomes and cell death pathways, also participates in the host response. Inflammasomes formed in response to microbial compounds typically involve complex formation with NOD-like receptors (NLRs), often an adapter called Asc and inflammatory caspases such as caspase-1. Activation leads to the generation of active caspase and subsequent cleavage of pro-IL-1b and pro-IL-18 into mature IL-1b/IL-18, key cytokines in many inflammatory responses, and cleavage of Gasdermin D, generating membrane pores during pyroptotic cell death. A number of pathogens may attempt to evade or minimize signaling via TLRs and NLRs, as this may be beneficial from a pathogen point of view.

Two methods Gram-negative pathogens may use for evasion are "stealth" by modifying their LPS, and active manipulation of host signaling by their type III secretion systems. However, this latter type of "pathological activity" can also be sensed by the host and lead to backup mechanisms. Increasingly, it is recognized that a great deal of cross-talk exists in innate immunity between different inflammatory and cell death pathways. One such example is from our work suggests that elements of extrinsic apoptosis, such as RIPK1 and caspase-8, can trigger mechanisms involving pyroptotic cell death and inflammasomes. A greater understanding of microbial activation and evasion of innate immunity can lead to new therapies and vaccines against infectious diseases.

One of the model systems we utilize involves bacteria of the genus Yersiniae, such as Yersinia pestis, the causative agents of plague, and the other human-pathogenic Yersinia, Y. pseudotuberculosis and Y. enterocolitica. We are also interested in innate immune responses to other pathogens such as Salmonella, Klebsiella, E. coli, SARS-CoV-2 and cytomegalovirus, and in understanding mechanisms of adjuvant action for vaccines. Other topics of interest are inflammation during IBD, obesity/diabetes and neurological diseases.

 

Biography:

Norwegian Institute of Technology (NTH), M.Sc. 1992

Norwegian University of Science and Technology (NTNU); Ph.D. 1998

Boston University/Boston Medical Center; Postdoc 1997-99

NTNU; Postdoc 1999-2001

UMass Medical School; Assistant Professor of Medicine, Department of Medicine, Division of Infectious Diseases and Immunology, 2002-2007

UMass Medical School; Associate Professor of Medicine and Microbiology and Physiological Systems 2007-2016

UMass Medical School; Professor (tenured) of Medicine, and Microbiology and Physiological Systems 2016-present

NTNU; Associate Professor II, 2008-2011

NTNU; Professor II, 2011-present

 

One or more keywords matched the following items that are connected to Lien, Egil
Item TypeName
Academic Article Lipopolysaccharide recognition, CD14, and lipopolysaccharide receptors.
Academic Article Differential roles of TLR2 and TLR4 in the host response to Gram-negative bacteria: lessons from a lipopolysaccharide-deficient mutant of Neisseria meningitidis.
Academic Article Response to Neisseria gonorrhoeae by cervicovaginal epithelial cells occurs in the absence of toll-like receptor 4-mediated signaling.
Academic Article Lipopolysaccharide rapidly traffics to and from the Golgi apparatus with the toll-like receptor 4-MD-2-CD14 complex in a process that is distinct from the initiation of signal transduction.
Academic Article Toll-like receptors and their function in innate and adaptive immunity.
Academic Article Injury primes the innate immune system for enhanced Toll-like receptor reactivity.
Academic Article A dinucleotide motif in oligonucleotides shows potent immunomodulatory activity and overrides species-specific recognition observed with CpG motif.
Academic Article Adjuvants and their signaling pathways: beyond TLRs.
Academic Article Increased expression of toll-like receptor 2 on monocytes in HIV infection: possible roles in inflammation and viral replication.
Academic Article TLR activation synergizes with Kilham rat virus infection to induce diabetes in BBDR rats.
Academic Article A mechanism for neurodegeneration induced by group B streptococci through activation of the TLR2/MyD88 pathway in microglia.
Academic Article Toll-like receptor 3 associates with c-Src tyrosine kinase on endosomes to initiate antiviral signaling.
Academic Article MD-2 expression is not required for cell surface targeting of Toll-like receptor 4 (TLR4).
Academic Article Virulence factors of Yersinia pestis are overcome by a strong lipopolysaccharide response.
Academic Article TLR9-signaling pathways are involved in Kilham rat virus-induced autoimmune diabetes in the biobreeding diabetes-resistant rat.
Academic Article Phagocytosis and intracellular killing of MD-2 opsonized gram-negative bacteria depend on TLR4 signaling.
Academic Article Cellular trafficking of lipoteichoic acid and Toll-like receptor 2 in relation to signaling: role of CD14 and CD36.
Academic Article Toll-like receptors.
Academic Article Inflammatory response after open heart surgery: release of heat-shock protein 70 and signaling through toll-like receptor-4.
Academic Article Differential gene expression downstream of Toll-like receptors (TLRs): role of c-Src and activating transcription factor 3 (ATF3).
Academic Article TLR4 is a negative regulator in noninfectious lung inflammation.
Academic Article The Rab11a GTPase controls Toll-like receptor 4-induced activation of interferon regulatory factor-3 on phagosomes.
Academic Article Toll-like receptor 3-elicited MAPK activation induces stabilization of interferon-? mRNA.
Academic Article Involvement of toll-like receptor (TLR) 2 and TLR4 in cell activation by mannuronic acid polymers.
Academic Article Hemagglutinin protein of wild-type measles virus activates toll-like receptor 2 signaling.
Academic Article Cellular activation, phagocytosis, and bactericidal activity against group B streptococcus involve parallel myeloid differentiation factor 88-dependent and independent signaling pathways.
Academic Article The NLRP3 inflammasome is up-regulated in cardiac fibroblasts and mediates myocardial ischaemia-reperfusion injury.
Academic Article Cell distributions and functions of Toll-like receptor 4 studied by fluorescent gene constructs.
Academic Article TLR9 signals after translocating from the ER to CpG DNA in the lysosome.
Academic Article Innate immune recognition of invasive bacteria accelerates atherosclerosis in apolipoprotein E-deficient mice.
Academic Article Lipopolysaccharide and double-stranded RNA up-regulate toll-like receptor 2 independently of myeloid differentiation factor 88.
Academic Article Soluble toll-like receptor 2 in HIV infection: association with disease progression.
Academic Article MyD88- and Bruton's tyrosine kinase-mediated signals are essential for T cell-independent pathogen-specific IgM responses.
Academic Article Evaluation of the role of LcrV-Toll-like receptor 2-mediated immunomodulation in the virulence of Yersinia pestis.
Academic Article Recruitment and endo-lysosomal activation of TLR9 in dendritic cells infected with Trypanosoma cruzi.
Academic Article Yersinia pestis evades TLR4-dependent induction of IL-12(p40)2 by dendritic cells and subsequent cell migration.
Academic Article The role of Toll-like receptor pathways in the mechanism of type 1 diabetes.
Academic Article MD-2-mediated ionic interactions between lipid A and TLR4 are essential for receptor activation.
Academic Article Toll-like receptor 2 deficiency results in impaired antibody responses and septic shock during Borrelia hermsii infection.
Academic Article UNC93B1 mediates host resistance to infection with Toxoplasma gondii.
Concept Toll-Like Receptors
Concept Toll-Like Receptor 4
Concept Toll-Like Receptor 9
Concept Toll-Like Receptor 3
Concept Toll-Like Receptor 2
Concept Toll-Like Receptor 5
Concept Toll-Like Receptor 1
Concept Toll-Like Receptor 8
Academic Article Induction of diabetes in the RIP-B7.1 mouse model is critically dependent on TLR3 and MyD88 pathways and is associated with alterations in the intestinal microbiome.
Academic Article Contribution of TLR4 and MyD88 for adjuvant monophosphoryl lipid A (MPLA) activity in a DNA prime-protein boost HIV-1 vaccine.
Academic Article A role for the adaptor proteins TRAM and TRIF in toll-like receptor 2 signaling.
Academic Article Mammalian Lipopolysaccharide Receptors Incorporated into the Retroviral Envelope Augment Virus Transmission.
Academic Article Toll-like receptors.
Academic Article Palmitate promotes inflammatory responses and cellular senescence in cardiac fibroblasts.
Academic Article Complement component C3 and the TLR co-receptor CD14 are not involved in angiotensin II induced cardiac remodelling.
Academic Article Caspase-8 mediates inflammation and disease in rodent malaria.
Search Criteria
  • Toll Like Receptors