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Cord factor

May 02, 2024

Cord factor, or trehalose dimycolate (TDM), is a glycolipid molecule found in the cell wall of Mycobacterium tuberculosis and similar species. It is the primary lipid found on the exterior of M. tuberculosis cells.[1] Cord factor influences the arrangement of M. tuberculosis cells into long and slender formations, giving its name.[2] Cord factor is virulent towards mammalian cells and critical for survival of M. tuberculosis in hosts, but not outside of hosts.[3][4] Cord factor has been observed to influence immune responses, induce the formation of granulomas, and inhibit tumor growth.[5] The antimycobacterial drug SQ109 is thought to inhibit TDM production levels and in this way disrupts its cell wall assembly.[6]

Cord factor
Identifiers
  • 61512-20-7 N
3D model (JSmol)
  • Interactive image
  • 451713
  • CCCCCCCCCCCCCCCCCCCCCCCCCC(C(CCCCCCCCCCC1CC1CCCCCCCCCCCCCCCCCC)C(=O)OCC2C(C(C(C(O2)OC3C(C(C(C(O3)COC(=O)C(CCCCCCCCCCCCCCCCCCCCCCCC)C(CCCCCCCCCCCC4CC4CCCCCCCCCCCCCCCCCC)O)O)O)O)O)O)O)O
Properties
C130H250O15
Molar mass 2053.415 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YN ?)
Cording Mycobacterium tuberculosis (H37Rv strain) viewed with fluorescent microscopy

Structure edit

A cord factor molecule is composed of a sugar molecule, trehalose (a disaccharide), composed of two glucose molecules linked together. Trehalose is esterified to two mycolic acid residues.[7][8] One of the two mycolic acid residues is attached to the sixth carbon of one glucose, while the other mycolic acid residue is attached to the sixth carbon of the other glucose.[7] Therefore, cord factor is also named trehalose-6,6'-dimycolate.[7] The carbon chain of the mycolic acid residues vary in length depending on the species of bacteria it is found in, but the general range is 20 to 80 carbon atoms.[3] Cord factor's amphiphilic nature leads to varying structures when many cord factor molecules are in close proximity.[3] On a hydrophobic surface, they spontaneously form a crystalline monolayer.[9] This crystalline monolayer is extremely durable and firm; it is stronger than any other amphiphile found in biology.[10] This monolayer also forms in oil-water, plastic-water, and air-water surfaces.[1] In an aqueous environment free of hydrophobic surfaces, cord factor forms a micelle.[11] Furthermore, cord factor interlocks with lipoarabinomannan (LAM), which is found on the surface of M. tuberculosis cells as well, to form an asymmetrical bilayer.[1][12] These properties cause bacteria that produce cord factor to grow into long, intertwining filaments, giving them a rope- or cord-like appearance when stained and viewed through a microscope (hence the name).[13]

Evidence of virulence edit

 
Scanning electron micrograph of Mycobacterium tuberculosis

A large quantity of cord factor is found in virulent M. tuberculosis, but not in avirulent M. tuberculosis.[1] Furthermore, M. tuberculosis loses its virulence if its ability to produce cord factor molecules is compromised.[1] Consequently, when all lipids are removed from the exterior of M. tuberculosis cells, the survival of the bacteria is reduced within a host.[14] When cord factor is added back to those cells, M. tuberculosis survives at a rate similar to that of its original state.[14] Cord factor increases the virulence of tuberculosis in mice, but it has minimal effect on other infections.[1]

Biological function edit

The function of cord factor is highly dependent on what environment it is located, and therefore its conformation.[15] This is evident as cord factor is harmful when injected with an oil solution, but not when it is with a saline solution, even in very large amounts.[15] Cord factor protects M. tuberculosis from the defenses of the host.[1] Specifically, cord factor on the surface of M. tuberculosis cells prevents fusion between phagosomal vesicles containing the M. tuberculosis cells and the lysosomes that would destroy them.[5][16] The individual components of cord factor, the trehalose sugars and mycolic acid residues, are not able to demonstrate this activity; the cord factor molecules must be fully intact.[5] Esterase activity that targets cord factor results in the lysis of M. tuberculosis cells.[17] However, the M. tuberculosis cells must still be alive to prevent this fusion; heat-killed cells with cord factor are unable to prevent being digested.[16] This suggests an additional molecule from M. tuberculosis is required.[16] Regardless, cord factor's ability to prevent fusion is related to an increased hydration force or through steric hindrance.[5] Cord factor remains on the surface of M. tuberculosis cells until it associates with a lipid droplet, where it forms a monolayer.[15] Then, as cord factor is in a monolayer configuration, it has a different function; it becomes fatal or harmful to the host organism.[18] Macrophages can die when in contact with monolayers of cord factor, but not when cord factor is in other configurations.[1] As the monolayer surface area of cord factor increases, so does its toxicity.[19] The length of the carbon chain on cord factor has also shown to affect toxicity; a longer chain shows higher toxicity.[20] Furthermore, fibrinogen has shown to adsorb to monolayers of cord factor and act as a cofactor for its biological effects.[21]

Cord factor isolated from species of Nocardia has been shown to cause cachexia in mice. Severe muscle wasting occurred within 48 hours of the toxin being administered.[22]

Host responses and cytokines edit

Numerous responses that vary in effect result from cord factor's presence in host cells. After exposure to cord factor for 2 hours, 125 genes in the mouse genome are upregulated.[23] After 24 hours, 503 genes are upregulated, and 162 genes are downregulated.[23] The exact chemical mechanisms by which cord factor acts is not completely known. However, it is likely that the mycolic acids of cord factor must undergo a cyclopropyl modification to lead to a response from the host's immune system for initial infection.[24] Furthermore, the ester linkages in cord factor are important for its toxic effects.[25] There is evidence that cord factor is recognized by the Mincle receptor, which is found on macrophages.[26][27] An activated Mincle receptor leads to a pathway that ultimately results in the production of several cytokines.[28][29] These cytokines can lead to further cytokine production that promote inflammatory responses.[30] Cord factor, through the Mincle receptor, also causes the recruitment of neutrophils, which lead to pro-inflammatory cytokines as well.[31] However, there is also evidence that toll-like receptor 2 (TLR2) in conjunction with the protein MyD-88 is responsible for cytokine production rather than the Mincle receptor.[23]

Cord factor presence increases the production of the cytokines interleukin-12 (IL-12), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor (TNFα), and macrophage inflammatory protein-2 (MIP-2), which are all pro-inflammatory cytokines important for granuloma formation.[16][28][32] IL-12 is particularly important in the defense against M. tuberculosis; without it, M. tuberculosis spreads unhampered.[33][34] IL-12 triggers production of more cytokines through T cells and natural killer (NK) cells, while also leading to mature Th1 cells, and thus leading to immunity.[35] Then, with IL-12 available, Th1 cells and NK cells produce interferon gamma (IFN-γ) molecules and subsequently release them.[36] The IFN-γ molecules in turn activate macrophages.[37]

When macrophages are activated by cord factor, they can arrange into granulomas around M. tuberculosis cells.[15][38] Activated macrophages and neutrophils also cause an increase in vascular endothelial growth factor (VEGF), which is important for angiogenesis, a step in granuloma formation.[39] The granulomas can be formed either with or without T-cells, indicating that they can be foreign-body-type or hypersensitivity-type.[37] This means cord factor can stimulate a response by acting as a foreign molecule or by causing harmful reactions from the immune system if the host is already immunized.[37] Thus, cord factor can act as a nonspecific irritant or a T-cell dependent antigen.[37] Granulomas enclose M. tuberculosis cells to halt the bacteria from spreading, but they also allow the bacteria to remain in the host.[16] From there, the tissue can become damaged and the disease can transmit further with cord factor.[40] Alternatively, the activated macrophages can kill the M. tuberculosis cells through reactive nitrogen intermediates to remove the infection.[41]

Besides inducing granuloma formation, activated macrophages that result from IL-12 and IFN-γ are able to limit tumor growth.[42] Furthermore, cord factor's stimulation of TNF-α production, also known as cachectin, is also able to induce cachexia, or loss of weight, within hosts.[43][44] Cord factor also increases NADase activity in the host, and thus it lowers NAD; enzymes that require NAD decrease in activity accordingly.[3] Cord factor is thus able to obstruct oxidative phosphorylation and the electron transport chain in mitochondrial membranes.[3] In mice, cord factor has shown to cause atrophy in the thymus through apoptosis; similarly in rabbits, atrophy of the thymus and spleen occurred.[45][46] This atrophy occurs in conjunction with granuloma formation, and if granuloma formation is disturbed, so is the progression of atrophy.[46]

Scientific applications and uses edit

Infection by M. tuberculosis remains a serious problem in the world and knowledge of cord factor can be useful in controlling this disease.[24] For example, the glycoprotein known as lactoferrin is able to mitigate cytokine production and granuloma formation brought on by cord factor.[47] However, cord factor can serve as a useful model for all pathogenic glycolipids and therefore it can provide insight for more than just itself as a virulence factor.[11][48] Hydrophobic beads covered with cord factor are an effective tool for such research; they are able to reproduce an organism's response to cord factor from M. tuberculosis cells.[11][48] Cord factor beads are easily created and applied to organisms for study, and then easily recovered.[48]

It is possible to form cord factor liposomes through water emulsion; these liposomes are nontoxic and can be used to maintain a steady supply of activated macrophages.[49] Cord factor under proper control can potentially be useful in fighting cancer because IL-12 and IFN-γ are able to limit the growth of tumors.[50]

See also edit

References edit

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  2. ^ Saita, N.; Fujiwara, N.; Yano, I.; Soejima, K.; Kobayashi, K. (1 October 2000). "Trehalose 6,6'-Dimycolate (Cord Factor) of Mycobacterium tuberculosis Induces Corneal Angiogenesis in Rats". Infection and Immunity. 68 (10): 5991–5997. doi:10.1128/IAI.68.10.5991-5997.2000. PMC 101563. PMID 10992511.
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May 02, 2024
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Cord factor or trehalose dimycolate TDM is a glycolipid molecule found in the cell wall of Mycobacterium tuberculosis and similar species It is the primary lipid found on the exterior of M tuberculosis cells 1 Cord factor influences the arrangement of M tuberculosis cells into long and slender formations giving its name 2 Cord factor is virulent towards mammalian cells and critical for survival of M tuberculosis in hosts but not outside of hosts 3 4 Cord factor has been observed to influence immune responses induce the formation of granulomas and inhibit tumor growth 5 The antimycobacterial drug SQ109 is thought to inhibit TDM production levels and in this way disrupts its cell wall assembly 6 Cord factor Identifiers CAS Number 61512 20 7 N 3D model JSmol Interactive image PubChem CID 451713 SMILES CCCCCCCCCCCCCCCCCCCCCCCCCC C CCCCCCCCCCC1CC1CCCCCCCCCCCCCCCCCC C O OCC2C C C C O2 OC3C C C C O3 COC O C CCCCCCCCCCCCCCCCCCCCCCCC C CCCCCCCCCCCC4CC4CCCCCCCCCCCCCCCCCC O O O O O O O O Properties Chemical formula C 130H 250O 15 Molar mass 2053 415 g mol 1 Except where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa N verify what is Y N Infobox references Cording Mycobacterium tuberculosis H37Rv strain viewed with fluorescent microscopy Contents 1 Structure 2 Evidence of virulence 3 Biological function 4 Host responses and cytokines 5 Scientific applications and uses 6 See also 7 ReferencesStructure editA cord factor molecule is composed of a sugar molecule trehalose a disaccharide composed of two glucose molecules linked together Trehalose is esterified to two mycolic acid residues 7 8 One of the two mycolic acid residues is attached to the sixth carbon of one glucose while the other mycolic acid residue is attached to the sixth carbon of the other glucose 7 Therefore cord factor is also named trehalose 6 6 dimycolate 7 The carbon chain of the mycolic acid residues vary in length depending on the species of bacteria it is found in but the general range is 20 to 80 carbon atoms 3 Cord factor s amphiphilic nature leads to varying structures when many cord factor molecules are in close proximity 3 On a hydrophobic surface they spontaneously form a crystalline monolayer 9 This crystalline monolayer is extremely durable and firm it is stronger than any other amphiphile found in biology 10 This monolayer also forms in oil water plastic water and air water surfaces 1 In an aqueous environment free of hydrophobic surfaces cord factor forms a micelle 11 Furthermore cord factor interlocks with lipoarabinomannan LAM which is found on the surface of M tuberculosis cells as well to form an asymmetrical bilayer 1 12 These properties cause bacteria that produce cord factor to grow into long intertwining filaments giving them a rope or cord like appearance when stained and viewed through a microscope hence the name 13 Evidence of virulence edit nbsp Scanning electron micrograph of Mycobacterium tuberculosis A large quantity of cord factor is found in virulent M tuberculosis but not in avirulent M tuberculosis 1 Furthermore M tuberculosis loses its virulence if its ability to produce cord factor molecules is compromised 1 Consequently when all lipids are removed from the exterior of M tuberculosis cells the survival of the bacteria is reduced within a host 14 When cord factor is added back to those cells M tuberculosis survives at a rate similar to that of its original state 14 Cord factor increases the virulence of tuberculosis in mice but it has minimal effect on other infections 1 Biological function editThe function of cord factor is highly dependent on what environment it is located and therefore its conformation 15 This is evident as cord factor is harmful when injected with an oil solution but not when it is with a saline solution even in very large amounts 15 Cord factor protects M tuberculosis from the defenses of the host 1 Specifically cord factor on the surface of M tuberculosis cells prevents fusion between phagosomal vesicles containing the M tuberculosis cells and the lysosomes that would destroy them 5 16 The individual components of cord factor the trehalose sugars and mycolic acid residues are not able to demonstrate this activity the cord factor molecules must be fully intact 5 Esterase activity that targets cord factor results in the lysis of M tuberculosis cells 17 However the M tuberculosis cells must still be alive to prevent this fusion heat killed cells with cord factor are unable to prevent being digested 16 This suggests an additional molecule from M tuberculosis is required 16 Regardless cord factor s ability to prevent fusion is related to an increased hydration force or through steric hindrance 5 Cord factor remains on the surface of M tuberculosis cells until it associates with a lipid droplet where it forms a monolayer 15 Then as cord factor is in a monolayer configuration it has a different function it becomes fatal or harmful to the host organism 18 Macrophages can die when in contact with monolayers of cord factor but not when cord factor is in other configurations 1 As the monolayer surface area of cord factor increases so does its toxicity 19 The length of the carbon chain on cord factor has also shown to affect toxicity a longer chain shows higher toxicity 20 Furthermore fibrinogen has shown to adsorb to monolayers of cord factor and act as a cofactor for its biological effects 21 Cord factor isolated from species of Nocardia has been shown to cause cachexia in mice Severe muscle wasting occurred within 48 hours of the toxin being administered 22 Host responses and cytokines editNumerous responses that vary in effect result from cord factor s presence in host cells After exposure to cord factor for 2 hours 125 genes in the mouse genome are upregulated 23 After 24 hours 503 genes are upregulated and 162 genes are downregulated 23 The exact chemical mechanisms by which cord factor acts is not completely known However it is likely that the mycolic acids of cord factor must undergo a cyclopropyl modification to lead to a response from the host s immune system for initial infection 24 Furthermore the ester linkages in cord factor are important for its toxic effects 25 There is evidence that cord factor is recognized by the Mincle receptor which is found on macrophages 26 27 An activated Mincle receptor leads to a pathway that ultimately results in the production of several cytokines 28 29 These cytokines can lead to further cytokine production that promote inflammatory responses 30 Cord factor through the Mincle receptor also causes the recruitment of neutrophils which lead to pro inflammatory cytokines as well 31 However there is also evidence that toll like receptor 2 TLR2 in conjunction with the protein MyD 88 is responsible for cytokine production rather than the Mincle receptor 23 Cord factor presence increases the production of the cytokines interleukin 12 IL 12 interleukin 1 beta IL 1b interleukin 6 IL 6 tumor necrosis factor TNFa and macrophage inflammatory protein 2 MIP 2 which are all pro inflammatory cytokines important for granuloma formation 16 28 32 IL 12 is particularly important in the defense against M tuberculosis without it M tuberculosis spreads unhampered 33 34 IL 12 triggers production of more cytokines through T cells and natural killer NK cells while also leading to mature Th1 cells and thus leading to immunity 35 Then with IL 12 available Th1 cells and NK cells produce interferon gamma IFN g molecules and subsequently release them 36 The IFN g molecules in turn activate macrophages 37 When macrophages are activated by cord factor they can arrange into granulomas around M tuberculosis cells 15 38 Activated macrophages and neutrophils also cause an increase in vascular endothelial growth factor VEGF which is important for angiogenesis a step in granuloma formation 39 The granulomas can be formed either with or without T cells indicating that they can be foreign body type or hypersensitivity type 37 This means cord factor can stimulate a response by acting as a foreign molecule or by causing harmful reactions from the immune system if the host is already immunized 37 Thus cord factor can act as a nonspecific irritant or a T cell dependent antigen 37 Granulomas enclose M tuberculosis cells to halt the bacteria from spreading but they also allow the bacteria to remain in the host 16 From there the tissue can become damaged and the disease can transmit further with cord factor 40 Alternatively the activated macrophages can kill the M tuberculosis cells through reactive nitrogen intermediates to remove the infection 41 Besides inducing granuloma formation activated macrophages that result from IL 12 and IFN g are able to limit tumor growth 42 Furthermore cord factor s stimulation of TNF a production also known as cachectin is also able to induce cachexia or loss of weight within hosts 43 44 Cord factor also increases NADase activity in the host and thus it lowers NAD enzymes that require NAD decrease in activity accordingly 3 Cord factor is thus able to obstruct oxidative phosphorylation and the electron transport chain in mitochondrial membranes 3 In mice cord factor has shown to cause atrophy in the thymus through apoptosis similarly in rabbits atrophy of the thymus and spleen occurred 45 46 This atrophy occurs in conjunction with granuloma formation and if granuloma formation is disturbed so is the progression of atrophy 46 Scientific applications and uses editInfection by M tuberculosis remains a serious problem in the world and knowledge of cord factor can be useful in controlling this disease 24 For example the glycoprotein known as lactoferrin is able to mitigate cytokine production and granuloma formation brought on by cord factor 47 However cord factor can serve as a useful model for all pathogenic glycolipids and therefore it can provide insight for more than just itself as a virulence factor 11 48 Hydrophobic beads covered with cord factor are an effective tool for such research they are able to reproduce an organism s response to cord factor from M tuberculosis cells 11 48 Cord factor beads are easily created and applied to organisms for study and then easily recovered 48 It is possible to form cord factor liposomes through water emulsion these liposomes are nontoxic and can be used to maintain a steady supply of activated macrophages 49 Cord factor under proper control can potentially be useful in fighting cancer because IL 12 and IFN g are able to limit the growth of tumors 50 See also editNocardiaReferences edit a b c d e f g h Hunter RL Olsen MR Jagannath C Actor JK Autumn 2006 Multiple roles of cord factor in the pathogenesis of primary secondary and cavitary tuberculosis including a revised description of the pathology of secondary disease Annals of Clinical and Laboratory Science 36 4 371 86 PMID 17127724 Saita N Fujiwara N Yano I Soejima K Kobayashi K 1 October 2000 Trehalose 6 6 Dimycolate Cord Factor of Mycobacterium tuberculosis Induces Corneal Angiogenesis in Rats Infection and Immunity 68 10 5991 5997 doi 10 1128 IAI 68 10 5991 5997 2000 PMC 101563 PMID 10992511 a b c d e Rajni Rao N Meena LS 2011 Biosynthesis and Virulent Behavior of Lipids Produced by Mycobacterium tuberculosis LAM and Cord Factor An Overview Biotechnology Research International 2011 274693 doi 10 4061 2011 274693 PMC 3039431 PMID 21350659 Silva CL Ekizlerian SM Fazioli RA February 1985 Role of cord factor in the modulation of infection caused by mycobacteria The American Journal of Pathology 118 2 238 47 PMC 1887869 PMID 3881973 a b c d Spargo BJ Crowe LM Ioneda T Beaman BL Crowe JH Feb 1 1991 Cord factor alpha alpha trehalose 6 6 dimycolate inhibits fusion between phospholipid vesicles Proceedings of the National Academy of Sciences of the United States of America 88 3 737 40 Bibcode 1991PNAS 88 737S doi 10 1073 pnas 88 3 737 PMC 50888 PMID 1992465 TAHLAN K R WILSON D B KASTRINSKY K ARORA V NAIR E FISCHER S W BARNES J R WALKER D ALLAND C E BARRY a H I BOSHOFF SQ109 Targets MmpL3 a Membrane Transporter of Trehalose Monomycolate Involved in Mycolic Acid Donation to the Cell Wall Core of Mycobacterium tuberculosis Antimicrobial Agents and Chemotherapy 2012 03 16 vol 56 issue 4 s 1797 1809 DOI 10 1128 AAC 05708 11 http aac asm org cgi doi 10 1128 AAC 05708 11 a b c NOLL H BLOCH H ASSELINEAU J LEDERER E May 1956 The chemical structure of the cord factor of Mycobacterium tuberculosis Biochimica et Biophysica Acta 20 2 299 309 doi 10 1016 0006 3002 56 90289 x PMID 13328853 Jonsson B E Gilljam M Lindblad A Ridell M Wold A E Welinder Olsson C 21 March 2007 Molecular Epidemiology of Mycobacterium abscessus with Focus on Cystic Fibrosis Journal of Clinical Microbiology 45 5 1497 1504 doi 10 1128 JCM 02592 06 PMC 1865885 PMID 17376883 Retzinger GS Meredith SC Hunter RL Takayama K Kezdy FJ August 1982 Identification of the physiologically active state of the mycobacterial glycolipid trehalose 6 6 dimycolate and the role of fibrinogen in the biologic activities of trehalose 6 6 dimycolate monolayers Journal of Immunology 129 2 735 44 doi 10 4049 jimmunol 129 2 735 PMID 6806381 S2CID 45693526 Hunter RL Venkataprasad N Olsen MR September 2006 The role of trehalose dimycolate cord factor on morphology of virulent M tuberculosis in vitro Tuberculosis Edinburgh Scotland 86 5 349 56 doi 10 1016 j tube 2005 08 017 PMID 16343989 a b c Retzinger GS Meredith SC Takayama K Hunter RL Kezdy FJ Aug 10 1981 The role of surface in the biological activities of trehalose 6 6 dimycolate Surface properties and development of a model system The Journal of Biological Chemistry 256 15 8208 16 doi 10 1016 S0021 9258 18 43410 2 PMID 7263645 Brennan PJ 2003 Structure function and biogenesis of the cell wall of Mycobacterium tuberculosis Tuberculosis Edinburgh Scotland 83 1 3 91 7 doi 10 1016 s1472 9792 02 00089 6 PMID 12758196 Bartelt MA 2000 Diagnostic Bacteriology A Study Guide Philadelphia USA F A Davis Company p 500 ISBN 978 0 8036 0301 1 a b Indrigo J Hunter RL Jr Actor JK July 2002 Influence of trehalose 6 6 dimycolate TDM during mycobacterial infection of bone marrow macrophages Microbiology 148 Pt 7 1991 8 doi 10 1099 00221287 148 7 1991 PMID 12101287 a b c d Hunter Robert L Olsen Margaret Jagannath Chinnaswamy Actor Jeffrey K April 2006 Trehalose 6 6 Dimycolate and Lipid in the Pathogenesis of Caseating Granulomas of Tuberculosis in Mice The American Journal of Pathology 168 4 1249 1261 doi 10 2353 ajpath 2006 050848 PMC 1606544 PMID 16565499 a b c d e Indrigo J Hunter RL Jr Actor JK August 2003 Cord factor trehalose 6 6 dimycolate TDM mediates trafficking events during mycobacterial infection of murine macrophages Microbiology 149 Pt 8 2049 59 doi 10 1099 mic 0 26226 0 PMID 12904545 Yang Y Bhatti A Ke D Gonzalez Juarrero M Lenaerts A Kremer L Guerardel Y Zhang P Ojha A K 15 November 2012 Exposure to a Cutinase like Serine Esterase Triggers Rapid Lysis of Multiple Mycobacterial Species Journal of Biological Chemistry 288 1 382 392 doi 10 1074 jbc M112 419754 PMC 3537035 PMID 23155047 Schabbing RW Garcia A Hunter RL February 1994 Characterization of the trehalose 6 6 dimycolate surface monolayer by scanning tunneling microscopy Infection and Immunity 62 2 754 6 doi 10 1128 IAI 62 2 754 756 1994 PMC 186174 PMID 8300239 Geisel RE Sakamoto K Russell DG Rhoades ER Apr 15 2005 In vivo activity of released cell wall lipids of Mycobacterium bovis bacillus Calmette Guerin is due principally to trehalose mycolates Journal of Immunology 174 8 5007 15 doi 10 4049 jimmunol 174 8 5007 PMID 15814731 Fujita Y Okamoto Y Uenishi Y Sunagawa M Uchiyama T Yano I July 2007 Molecular and supra molecular structure related differences in toxicity and granulomatogenic activity of mycobacterial cord factor in mice Microbial Pathogenesis 43 1 10 21 doi 10 1016 j micpath 2007 02 006 PMID 17434713 Sakamoto K Geisel R E Kim M J Wyatt B T Sellers L B Smiley S T Cooper A M Russell D G Rhoades E R 22 December 2009 Fibrinogen Regulates the Cytotoxicity of Mycobacterial Trehalose Dimycolate but Is Not Required for Cell Recruitment Cytokine Response or Control of Mycobacterial Infection Infection and Immunity 78 3 1004 1011 doi 10 1128 IAI 00451 09 PMC 2825938 PMID 20028811 Silva C L Tincani I Filho S L B Faccioli L H 1988 06 01 Mouse Cachexia Induced by Trehalose Dimycolate from Nocardia asteroides Microbiology 134 6 1629 1633 doi 10 1099 00221287 134 6 1629 ISSN 1350 0872 a b c Sakamoto K Kim M J Rhoades E R Allavena R E Ehrt S Wainwright H C Russell D G Rohde K H 21 December 2012 Mycobacterial Trehalose Dimycolate Reprograms Macrophage Global Gene Expression and Activates Matrix Metalloproteinases Infection and Immunity 81 3 764 776 doi 10 1128 IAI 00906 12 PMC 3584883 PMID 23264051 a b Rao V Fujiwara N Porcelli SA Glickman MS Feb 21 2005 Mycobacterium tuberculosis controls host innate immune activation through cyclopropane modification of a glycolipid effector molecule The Journal of Experimental Medicine 201 4 535 43 doi 10 1084 jem 20041668 PMC 2213067 PMID 15710652 Kato M March 1970 Action of a toxic glycolipid of Corynebacterium diphtheriae on mitochondrial structure and function Journal of Bacteriology 101 3 709 16 doi 10 1128 JB 101 3 709 716 1970 PMC 250382 PMID 4314542 Ishikawa E Ishikawa T Morita YS Toyonaga K Yamada H Takeuchi O Kinoshita T Akira S Yoshikai Y Yamasaki S Dec 21 2009 Direct recognition of the mycobacterial glycolipid trehalose dimycolate by C type lectin Mincle The Journal of Experimental Medicine 206 13 2879 88 doi 10 1084 jem 20091750 PMC 2806462 PMID 20008526 Schoenen H Bodendorfer B Hitchens K Manzanero S Werninghaus K Nimmerjahn F Agger EM Stenger S Andersen P Ruland J Brown GD Wells C Lang R Mar 15 2010 Cutting edge Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose dibehenate Journal of Immunology 184 6 2756 60 doi 10 4049 jimmunol 0904013 PMC 3442336 PMID 20164423 a b Werninghaus K Babiak A Gross O Holscher C Dietrich H Agger E M Mages J Mocsai A Schoenen H Finger K Nimmerjahn F Brown G D Kirschning C Heit A Andersen P Wagner H Ruland J Lang R 12 January 2009 Adjuvanticity of a synthetic cord factor analogue for subunit Mycobacterium tuberculosis vaccination requires FcR Syk Card9 dependent innate immune activation Journal of Experimental Medicine 206 1 89 97 doi 10 1084 jem 20081445 PMC 2626670 PMID 19139169 Yamasaki S Ishikawa E Sakuma M Hara H Ogata K Saito T October 2008 Mincle is an ITAM coupled activating receptor that senses damaged cells Nature Immunology 9 10 1179 88 doi 10 1038 ni 1651 PMID 18776906 S2CID 205361789 Welsh K J Abbott A N Hwang S A Indrigo J Armitige L Y Blackburn M R Hunter R L Actor J K 1 June 2008 A role for tumour necrosis factor complement C5 and interleukin 6 in the initiation and development of the mycobacterial cord factor trehalose 6 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infected with mycobacterium tuberculosis The Journal of Experimental Medicine 186 1 39 45 doi 10 1084 jem 186 1 39 PMC 2198958 PMID 9206995 Trinchieri G 1995 Interleukin 12 a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen specific adaptive immunity Annual Review of Immunology 13 1 251 76 doi 10 1146 annurev iy 13 040195 001343 PMID 7612223 Magram Jeanne Connaughton Suzanne E Warrier Rajeev R Carvajal Daisy M Wu Chang you Ferrante Jessica Stewart Colin Sarmiento Ulla Faherty Denise A Gately Maurice K May 1996 IL 12 Deficient Mice Are Defective in IFNg Production and Type 1 Cytokine Responses Immunity 4 5 471 481 doi 10 1016 S1074 7613 00 80413 6 PMID 8630732 a b c d Yamagami H Matsumoto T Fujiwara N Arakawa T Kaneda K Yano I Kobayashi K February 2001 Trehalose 6 6 dimycolate cord factor of Mycobacterium tuberculosis induces foreign body and hypersensitivity type granulomas in mice Infection and Immunity 69 2 810 5 doi 10 1128 IAI 69 2 810 815 2001 PMC 97956 PMID 11159972 Bekierkunst A October 1968 Acute granulomatous response produced in mice by trehalose 6 6 dimycolate Journal of Bacteriology 96 4 958 61 doi 10 1128 JB 96 4 958 961 1968 PMC 252404 PMID 4971895 Sakaguchi I Ikeda N Nakayama M Kato Y Yano I Kaneda K April 2000 Trehalose 6 6 dimycolate Cord factor enhances neovascularization through vascular endothelial growth factor production by neutrophils and macrophages Infection and Immunity 68 4 2043 52 doi 10 1128 iai 68 4 2043 2052 2000 PMC 97384 PMID 10722600 Kobayashi Kazuo Kaneda Kenji Kasama Tsuyoshi 15 May 2001 Immunopathogenesis of delayed type hypersensitivity Microscopy Research and Technique 53 4 241 245 doi 10 1002 jemt 1090 PMID 11340669 S2CID 1851137 Chan J Xing Y Magliozzo RS Bloom BR Apr 1 1992 Killing of virulent Mycobacterium tuberculosis by reactive nitrogen intermediates produced by activated murine macrophages The Journal of Experimental Medicine 175 4 1111 22 doi 10 1084 jem 175 4 1111 PMC 2119182 PMID 1552282 Oswald IP Dozois CM Petit JF Lemaire G April 1997 Interleukin 12 synthesis is a required step in trehalose dimycolate induced activation of mouse peritoneal macrophages Infection and Immunity 65 4 1364 9 doi 10 1128 IAI 65 4 1364 1369 1997 PMC 175141 PMID 9119475 Semenzato G March 1990 Tumour necrosis factor a cytokine with multiple biological activities British Journal of Cancer 61 3 354 361 doi 10 1038 bjc 1990 78 PMC 1971301 PMID 2183871 Silva CL Faccioli LH December 1988 Tumor necrosis factor cachectin mediates induction of cachexia by cord factor from mycobacteria Infection and Immunity 56 12 3067 71 doi 10 1128 IAI 56 12 3067 3071 1988 PMC 259702 PMID 3053451 Hamasaki N Isowa K Kamada K Terano Y Matsumoto T Arakawa T Kobayashi K Yano I June 2000 In vivo administration of mycobacterial cord factor Trehalose 6 6 dimycolate can induce lung and liver granulomas and thymic atrophy in rabbits Infection and Immunity 68 6 3704 9 doi 10 1128 iai 68 6 3704 3709 2000 PMC 97662 PMID 10816531 a b Ozeki Y Kaneda K Fujiwara N Morimoto M Oka S Yano I May 1997 In vivo induction of apoptosis in the thymus by administration of mycobacterial cord factor trehalose 6 6 dimycolate Infection and Immunity 65 5 1793 9 doi 10 1128 IAI 65 5 1793 1799 1997 PMC 175219 PMID 9125563 Welsh Kerry J Hwang Shen An Hunter Robert L Kruzel Marian L Actor Jeffrey K October 2010 Lactoferrin modulation of mycobacterial cord factor trehalose 6 6 dimycolate induced granulomatous response Translational Research 156 4 207 215 doi 10 1016 j trsl 2010 06 001 PMC 2948024 PMID 20875896 a b c Retzinger GS April 1987 Dissemination of beads coated with trehalose 6 6 dimycolate a possible role for coagulation in the dissemination process Experimental and Molecular Pathology 46 2 190 8 doi 10 1016 0014 4800 87 90065 7 PMID 3556532 Lepoivre M Tenu JP Lemaire G Petit JF August 1982 Antitumor activity and hydrogen peroxide release by macrophages elicited by trehalose diesters Journal of Immunology 129 2 860 6 doi 10 4049 jimmunol 129 2 860 PMID 6806386 Oswald IP Afroun S Bray D Petit JF Lemaire G September 1992 Low response of BALB c macrophages to priming and activating signals Journal of Leukocyte Biology 52 3 315 22 doi 10 1002 jlb 52 3 315 PMID 1381743 S2CID 2190434 Retrieved from https en wikipedia org w index php title Cord factor amp oldid 1195162973, wikipedia, wiki, book, books, library,

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