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Medzhitov R

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https://www.readbyqxmd.com/read/26829621/training-the-next-generation-of-biomedical-investigators-in-glycosciences
#1
REVIEW
Peter Agre, Carolyn Bertozzi, Mina Bissell, Kevin P Campbell, Richard D Cummings, Umesh R Desai, Mary Estes, Terence Flotte, Guy Fogleman, Fred Gage, David Ginsburg, Jeffrey I Gordon, Gerald Hart, Vincent Hascall, Laura Kiessling, Stuart Kornfeld, John Lowe, John Magnani, Lara K Mahal, Ruslan Medzhitov, Richard J Roberts, Robert Sackstein, Rita Sarkar, Ronald Schnaar, Nancy Schwartz, Ajit Varki, David Walt, Irving Weissman
This position statement originated from a working group meeting convened on April 15, 2015, by the NHLBI and incorporates follow-up contributions by the participants as well as other thought leaders subsequently consulted, who together represent research fields relevant to all branches of the NIH. The group was deliberately composed not only of individuals with a current research emphasis in the glycosciences, but also of many experts from other fields, who evinced a strong interest in being involved in the discussions...
February 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/25043024/functional-polarization-of-tumour-associated-macrophages-by-tumour-derived-lactic-acid
#2
Oscar R Colegio, Ngoc-Quynh Chu, Alison L Szabo, Thach Chu, Anne Marie Rhebergen, Vikram Jairam, Nika Cyrus, Carolyn E Brokowski, Stephanie C Eisenbarth, Gillian M Phillips, Gary W Cline, Andrew J Phillips, Ruslan Medzhitov
Macrophages have an important role in the maintenance of tissue homeostasis. To perform this function, macrophages must have the capacity to monitor the functional states of their 'client cells': namely, the parenchymal cells in the various tissues in which macrophages reside. Tumours exhibit many features of abnormally developed organs, including tissue architecture and cellular composition. Similarly to macrophages in normal tissues and organs, macrophages in tumours (tumour-associated macrophages) perform some key homeostatic functions that allow tumour maintenance and growth...
September 25, 2014: Nature
https://www.readbyqxmd.com/read/22896629/semaphorin-7a-contributes-to-west-nile-virus-pathogenesis-through-tgf-%C3%AE-1-smad6-signaling
#3
Hameeda Sultana, Girish Neelakanta, Harald G Foellmer, Ruth R Montgomery, John F Anderson, Raymond A Koski, Ruslan M Medzhitov, Erol Fikrig
Semaphorin 7A (Sema7A) is a membrane-associated/secreted protein that plays an essential role in connecting the vertebrate neuronal and immune systems. However, the role of Sema7A has not been elucidated in viral pathogenesis. In this study, we show that abrogation of Sema7A protects mice from lethal West Nile virus (WNV) infection. Mice lacking Sema7A showed increased survival, reduced viral burden, and less blood-brain barrier permeability upon WNV infection. Increased Sema7A levels were evident in murine tissues, as well as in murine cortical neurons and primary human macrophages upon WNV infection...
September 15, 2012: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/20333437/control-of-infection-by-pyroptosis-and-autophagy-role-of-tlr-and-nlr
#4
Karina R Bortoluci, Ruslan Medzhitov
Cells can die by distinct mechanisms with particular impacts on the immune response. In addition to apoptosis and necrosis, recent studies lead to characterization of a new proinflammatory form of cell death, pyroptosis. TLR and NLR, central innate immune sensors, can control infections by modulating host cell survival. In addition, TLRs can promote the induction of autophagy, thus promoting delivery of infecting pathogens to the lysosomes. On the other hand, activation of some NLR members, especially NLRC4 and NAIP5, leads to the infected cell death by pyroptosis, which is accompanied by secretion of the proinflammatory cytokines IL-1beta, IL-18, and IL-33...
March 24, 2010: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/20229126/control-of-infection-by-pyroptosis-and-autophagy-role-of-tlr-and-nlr
#5
REVIEW
Karina R Bortoluci, Ruslan Medzhitov
Cells can die by distinct mechanisms with particular impacts on the immune response. In addition to apoptosis and necrosis, recent studies lead to characterization of a new pro-inflammatory form of cell death, pyroptosis. TLR and NLR, central innate immune sensors, can control infections by modulating host cell survival. In addition, TLRs can promote the induction of autophagy, thus promoting delivery of infecting pathogens to the lysosomes. On the other hand, activation of some NLR members, especially NLRC4 and NAIP5, leads to the infected cell death by pyroptosis, which is accompanied by secretion of the pro-inflammatory cytokines IL-1beta, IL-18, and IL-33...
May 2010: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/20072123/emerging-functions-of-basophils-in-protective-and-allergic-immune-responses
#6
REVIEW
C L Sokol, R Medzhitov
Basophils that were long thought to have a redundant role in mast cells in the effector response to allergens and parasites are now being recognized to have important roles in the regulation of adaptive immune responses. Recent data have revealed their role in the initiation of the T helper cell 2 (Th2)-mediated immune response. Not only do basophils guide the Th1-Th2 balance by providing an early source of crucial Th2-skewing cytokines, interleukin (IL)-4 and thymic stromal lymphopoietin, but recent findings have also illustrated their capacity to function as antigen-presenting cells...
March 2010: Mucosal Immunology
https://www.readbyqxmd.com/read/19079220/innate-immune-recognition-of-the-indigenous-microbial-flora
#7
REVIEW
S Rakoff-Nahoum, R Medzhitov
Our studies have focused on understanding the mechanisms of interactions between the indigenous intestinal flora and the mammalian host in both physiological and nonphysiological conditions. In particular, we have focused on the function of innate microbial pattern recognition by Toll-like receptors in the context of tissue injury and repair, spontaneous colitis, and postnatal development.
November 2008: Mucosal Immunology
https://www.readbyqxmd.com/read/18605980/role-of-toll-like-receptors-in-tissue-repair-and-tumorigenesis
#8
REVIEW
S Rakoff-Nahoum, R Medzhitov
Toll-like receptors (TLRs) play a critical role in host defense from microbial infection. TLRs recognize conserved molecular structures produced by microorganisms and induce activation of innate and adaptive immune responses. The inflammatory responses induced by TLRs play an important role TLRs not only in host defense from infection, but also in tissue repair and regeneration. This latter function of TLRs can also contribute to tumorigenesis. Here we review recent progress in understanding the role of TLRs in cancer development...
May 2008: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/18187568/lupus-nephritis-the-central-role-of-nucleosomes-revealed
#9
REVIEW
Elin S Mortensen, Kristin A Fenton, Ole P Rekvig
Systemic lupus erythematosus (SLE) is an autoimmune syndrome characterized by autoantibodies to nuclear constituents. Some of these antibodies are diagnostically important, whereas others act as disease-modifying factors. One clinically important factor is autoantibodies against dsDNA and nucleosomes, which have overlapping diagnostic and nephritogenic impact in SLE. Although a scientific focus for 5 decades, the molecular and cellular origin of these antibodies, and why they are associated with lupus nephritis, is still not fully understood...
February 2008: American Journal of Pathology
https://www.readbyqxmd.com/read/17202359/age-associated-defect-in-human-tlr-1-2-function
#10
David van Duin, Subhasis Mohanty, Venetta Thomas, Sandra Ginter, Ruth R Montgomery, Erol Fikrig, Heather G Allore, Ruslan Medzhitov, Albert C Shaw
The effects of aging on human TLR function remain incompletely understood. We assessed TLR function and expression in peripheral blood monocytes from 159 subjects in 2 age categories, 21-30 and >65 years of age, using a multivariable mixed effect model. Using flow cytometry to assess TLR-induced cytokine production, we observed a substantial, highly significant defect in TLR1/2-induced TNF-alpha (p = 0.0003) and IL-6 (p < 0.0001) production, in older adults compared with young controls. In contrast to findings in aged mice, other TLR (including TLR2/6)-induced cytokine production appeared largely intact...
January 15, 2007: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/16922084/role-of-the-innate-immune-system-and-host-commensal-mutualism
#11
REVIEW
S Rakoff-Nahoum, R Medzhitov
Host organisms live in intimate contact with indigenous microflora. The interactions between the host and commensal microbiota are highly complex and heterogeneous. A growing body of evidence indicates that commensal symbionts provide many benefits to the host physiology, particularly in the gastrointestinal system. The molecular mechanisms of the mutualistic interactions between the host and commensals are largely unknown but can be due either to bioactivity of the commensals or to the reaction of the host immune system to the commensal-derived products...
2006: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/16244651/regulation-of-lung-injury-and-repair-by-toll-like-receptors-and-hyaluronan
#12
COMPARATIVE STUDY
Dianhua Jiang, Jiurong Liang, Juan Fan, Shuang Yu, Suping Chen, Yi Luo, Glenn D Prestwich, Marcella M Mascarenhas, Hari G Garg, Deborah A Quinn, Robert J Homer, Daniel R Goldstein, Richard Bucala, Patty J Lee, Ruslan Medzhitov, Paul W Noble
Mechanisms that regulate inflammation and repair after acute lung injury are incompletely understood. The extracellular matrix glycosaminoglycan hyaluronan is produced after tissue injury and impaired clearance results in unremitting inflammation. Here we report that hyaluronan degradation products require MyD88 and both Toll-like receptor (TLR)4 and TLR2 in vitro and in vivo to initiate inflammatory responses in acute lung injury. Hyaluronan fragments isolated from serum of individuals with acute lung injury stimulated macrophage chemokine production in a TLR4- and TLR2-dependent manner...
November 2005: Nature Medicine
https://www.readbyqxmd.com/read/12618855/toll-like-receptors-and-their-role-in-experimental-models-of-microbial-infection
#13
REVIEW
Salman T Qureshi, R Medzhitov
Effective host defense against microbial infection depends upon prompt recognition of pathogens, activation of immediate containment measures, and ultimately the generation of a specific and definitive adaptive immune response. The innate immune system of the host is responsible for providing constant surveillance against infection; when confronted by pathogens it deploys a series of rapidly acting antimicrobial effectors while simultaneously instructing the adaptive immune system as to the nature and context of the infectious threat...
March 2003: Genes and Immunity
https://www.readbyqxmd.com/read/12467245/toll-like-receptors-and-their-ligands
#14
REVIEW
G M Barton, R Medzhitov
The Toll-like receptors (TLRs) are key molecules involved in the recognition of pathogens by the innate immune system. This family of germ line-encoded receptors has evolved to recognize conserved features of microbes. Currently, 10 TLR family members have been identified in mammals. The number of ligands for these receptors continues to grow, and it seems clear that multiple ligands exist for each receptor. Whether engagement of different TLRs leads to differences in gene expression and thereby differences in the immune response remains to be seen...
2002: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/11905821/toll-like-receptors-and-innate-immunity
#15
REVIEW
R Medzhitov
Toll-like receptors have a crucial role in the detection of microbial infection in mammals and insects. In mammals, these receptors have evolved to recognize conserved products unique to microbial metabolism. This specificity allows the Toll proteins to detect the presence of infection and to induce activation of inflammatory and antimicrobial innate immune responses. Recognition of microbial products by Toll-like receptors expressed on dendritic cells triggers functional maturation of dendritic cells and leads to initiation of antigen-specific adaptive immune responses...
November 2001: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/11724812/evolutionary-perspective-on-innate-immune-recognition
#16
REVIEW
A Mushegian, R Medzhitov
Analysis of human and Drosophila genomes demonstrates an ancient origin of innate immunity and the diversity of the mechanisms of innate immune recognition.
November 26, 2001: Journal of Cell Biology
https://www.readbyqxmd.com/read/11607032/recognition-of-double-stranded-rna-and-activation-of-nf-kappab-by-toll-like-receptor-3
#17
L Alexopoulou, A C Holt, R Medzhitov, R A Flavell
Toll-like receptors (TLRs) are a family of innate immune-recognition receptors that recognize molecular patterns associated with microbial pathogens, and induce antimicrobial immune responses. Double-stranded RNA (dsRNA) is a molecular pattern associated with viral infection, because it is produced by most viruses at some point during their replication. Here we show that mammalian TLR3 recognizes dsRNA, and that activation of the receptor induces the activation of NF-kappaB and the production of type I interferons (IFNs)...
October 18, 2001: Nature
https://www.readbyqxmd.com/read/11606776/drosophila-myd88-is-an-adapter-in-the-toll-signaling-pathway
#18
T Horng, R Medzhitov
Toll-like receptors comprise a family of cell surface receptors that play a crucial role in the innate immune recognition of both Drosophila and mammals. Previous studies have shown that Drosophila Toll-1 mediates the induction of antifungal peptides during fungal infection of adult flies. Through genetic studies, Tube, Pelle, Cactus, and Dif have been identified as downstream components of the Toll-1 signaling pathway. Here we report characterization of a Drosophila homologue of human MyD88, dMyD88. We show that dMyD88 is an adapter in the Toll signaling pathway that associates with both the Toll receptor and the downstream kinase Pelle...
October 23, 2001: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/11547333/toll-like-receptors-control-activation-of-adaptive-immune-responses
#19
M Schnare, G M Barton, A C Holt, K Takeda, S Akira, R Medzhitov
Mechanisms that control the activation of antigen-specific immune responses in vivo are poorly understood. It has been suggested that the initiation of adaptive immune responses is controlled by innate immune recognition. Mammalian Toll-like receptors play an essential role in innate immunity by recognizing conserved pathogen-associated molecular patterns and initiating the activation of NF-kappaB and other signaling pathways through the adapter protein, MyD88. Here we show that MyD88-deficient mice have a profound defect in the activation of antigen-specific T helper type 1 (TH1) but not TH2 immune responses...
October 2001: Nature Immunology
https://www.readbyqxmd.com/read/11526399/tirap-an-adapter-molecule-in-the-toll-signaling-pathway
#20
T Horng, G M Barton, R Medzhitov
Mammalian Toll-like receptors (TLRs) recognize conserved products of microbial metabolism and activate NF-kappa B and other signaling pathways through the adapter protein MyD88. Although some cellular responses are completely abolished in MyD88-deficient mice, TLR4, but not TLR9, can activate NF-kappa B and mitogen-activated protein kinases and induce dendritic cell maturation in the absence of MyD88. These differences suggest that another adapter must exist that can mediate MyD88-independent signaling in response to TLR4 ligation...
September 2001: Nature Immunology
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