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Research Interests:

Pathogen activation and evasion of innate immune signaling - Inflammasomes and Toll-like Receptors.

Over the last several years, 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 the innate immune recognition of pathogens by Toll-like receptors (TLRs) and inflammasomes. Lipopolysaccharide (LPS) from Gram-negative bacteria (also called endotoxin) is particularly interesting, it is a saccharide containing acyl chains (“fatty sugar”). LPS is a main component of the Gram-negative outer membrane, and one of the most potent activators of immune cells. LPS activation of host cells is a double-edged sword: An early sensing of LPS is important for clearance of an initial Gram-negative infection, but high amounts of LPS in circulation during overwhelming bacteremia and sepsis can lead to Gram-negative endotoxic shock and death. Thus, a well timed, balanced and measured host response to LPS is critical in determining outcome of an infection. LPS activates cells via TLR4 and MD-2, but recognition of other microbial components, such as those mediated by inflammasomes, also participates in an optimal host response. Inflammasomes formed in response to microbial compounds typically involve complex formation with NOD-like receptors (NLRs) such as NLRP3, NLRP12 or NLRC4, 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. A number of pathogens may attempt to minimize signaling via TLRs and NLRs, as this may be beneficial from a pathogen point of view. 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. Y. pestis, a master of immune evasion, normally produces tetra-acylated LPS with low ability to trigger TLR4 signaling. However, the activation potential can be restored upon the forced generation of a hexa-acylated LPS similar to that found in Y. pseudotuberculosis, and this markedly attenuates Y. pestis in vivo, suggesting a role for evasion of TLR4 signaling in the evolution of high virulence in plague. IL-1b and in particular IL-18 appear to be effective mediators of antibacterial defenses against Y. pestis, and NLR containing inflammasomes participate in optimal IL-18 and IL-1b production. We are also interested in innate immune responses to other pathogens such as Salmonella, Klebsiella, E. coli and cytomegalovirus, and in understanding mechanisms of adjuvant action for Yersinia, HIV-1 and malaria vaccines. Another topic we study is inflammation involved in the development of diabetes and obesity.

 

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 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 Response to Neisseria gonorrhoeae by cervicovaginal epithelial cells occurs in the absence of toll-like receptor 4-mediated signaling.
Academic Article Injury primes the innate immune system for enhanced Toll-like receptor reactivity.
Academic Article The LPS receptor generates inflammatory signals from the cell surface.
Academic Article Increased expression of toll-like receptor 2 on monocytes in HIV infection: possible roles in inflammation and viral replication.
Academic Article TLR9-signaling pathways are involved in Kilham rat virus-induced autoimmune diabetes in the biobreeding diabetes-resistant rat.
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 Inflammation and fibrosis during Chlamydia pneumoniae infection is regulated by IL-1 and the NLRP3/ASC inflammasome.
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 The NLRP3 inflammasome is up-regulated in cardiac fibroblasts and mediates myocardial ischaemia-reperfusion injury.
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 Yersinia pestis evades TLR4-dependent induction of IL-12(p40)2 by dendritic cells and subsequent cell migration.
Academic Article NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals.
Academic Article UNC93B1 mediates host resistance to infection with Toxoplasma gondii.
Academic Article The NLRP12 inflammasome recognizes Yersinia pestis.
Concept Interleukin-10
Concept Interleukin-1
Concept Interleukin 1 Receptor Antagonist Protein
Concept Interleukin-1beta
Concept Interleukin-8
Concept Interleukin-12 Subunit p40
Concept Interleukin-6
Concept Receptors, Interleukin
Concept Interleukin-18
Concept Interleukin-12
Academic Article RNA and ß-hemolysin of group B Streptococcus induce interleukin-1ß (IL-1ß) by activating NLRP3 inflammasomes in mouse macrophages.
Academic Article A role for the adaptor proteins TRAM and TRIF in toll-like receptor 2 signaling.
Academic Article Absence of the inflammasome adaptor ASC reduces hypoxia-induced pulmonary hypertension in mice.
Academic Article Manipulation of Interleukin-1ß and Interleukin-18 Production by Yersinia pestis Effectors YopJ and YopM and Redundant Impact on Virulence.
Academic Article Early Upregulation of NLRP3 in the Brain of Neonatal Mice Exposed to Hypoxia-Ischemia: No Early Neuroprotective Effects of NLRP3 Deficiency.
Academic Article Mammalian Lipopolysaccharide Receptors Incorporated into the Retroviral Envelope Augment Virus Transmission.
Academic Article Palmitate promotes inflammatory responses and cellular senescence in cardiac fibroblasts.
Academic Article Streptolysin O Induces the Ubiquitination and Degradation of Pro-IL-1ß.
Academic Article NLRP3 inflammasome mediates oxidative stress-induced pancreatic islet dysfunction.

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