| Post: | Lecturer in Immunology |
| Location: | JMS Building |
| Email: | M.Triantafilou@sussex.ac.uk |
| Telephone numbers | |
| Internal: | 8362 or 8923 |
| UK: | (01273) 678362 or (01273) 678923 |
| International: | +44 1273 678362 or +44 1273 678923 |
Biography
External activities
Member of the International Endotoxin and Innate Immunity Society
Member of the American Society for Microbiology
Member of the British Society of Immunology
Role
Admissions Tutor for the Department of Biochemistry and Biomedical Sciences
Research
The research focus of the Infection and Immunity group is host-pathogen interactions and, in particular, the innate recognition of bacteria and interactions of viruses with the immune system.
The innate immune response protects host organisms against invading pathogens prior to the onset of adaptive immunity. Innate responses are often critical in determining the ultimate outcome of infection or success of vaccination, and uncontrolled inflammatory responses can cause serious immune-mediated pathology. Microorganisms that invade a vertebrate host are initially recognized by the innate immune system through germline-encoded pattern-recognition receptors (PRRs).
Significant advances in our understanding of the innate immune recognition have been made in the last decade following the identification of three families of pattern recognition receptors: Toll-like receptors (TLRs), NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs). TLRs are pattern recognition receptors that detect motifs or signatures from bacteria, viruses, protozoa and fungi. NLRs detect mainly intracellular bacteria and RLRs detect viral genome. These three families of pattern recognition receptors comprise the front line of defence that the host possesses against microbial pathogens.
Over the past few years our research group has been focusing on unravelling the molecular mechanisms behind the innate recognition of viral pathogens by PRRs. In particular, we have focused on the involvement of the Toll-like receptor (TLR) family of proteins as well as RIG-I-like receptors (RLRs) in the innate immune sensing of viruses.
We have uniquely combined techniques -- from immunology, biochemistry, proteomics, molecular biology and biophysics to explore the interaction of pathogens with TLRs and RLRs. We have the expertise and the research tools for investigating innate immune mechanisms. Using combinations of these techniques, our group has previously discovered novel concepts in innate immune recognition of microbial ligands by TLRs and co-operating PRRs. Among others, our major discoveries in the field of innate immune recognition of viral pathogens include:
- Showing that TLR4 (Triantafilou & Triantafilou 2004) is involved in the innate immune sensing of Coxsackievirus B4.
- Demonstrating that TLR7 and TLR8 (Triantafilou et al. 2005a;Triantafilou et al. 2005b) are involved in sensing viral products. These were the first studies to reveal how enteroviruses are recognised by the innate immune system.
Our major interests relate to the ability of the innate immune system to recognize the presence of microbial pathogens and respond to them. Our research is focused on understanding how pattern recognition receptors sense microbes and trigger innate immunity. PRRs include retinoic acid-inducible gene (RIG-I)-like receptors (RLRs) and Toll-like receptors (TLRs). In particular, we are interested in:
- Understanding the interaction of microbial pathogens with host PRRs and subsequent signaling pathways in immune cells
- Studying the cross-talk among PRR pathways and the regulation of downstream genes after exposure to virus
- Profiling the responses of innate immune cells after viral infection
References
Triantafilou, K., Orthopoulos, G., Vakakis, E., Ahmed, M. A. E., Golenbock, D. T., Lepper, P. M., & Triantafilou, M. 2005a, "Human cardiac inflammatory responses triggered by Coxsackie B Viruses are mainly Toll-like receptor (TLR) 8-dependent", Cellular Microbiol 7, 1117-1126.
Triantafilou, K. & Triantafilou, M. 2004, "Coxsackievirus B4-induced cytokine production in pancreatic cells is mediated through TLR4", J Virol, vol. 78, pp. 11313-11320.
Triantafilou, K., Vakakis, E., Orthopoulos, G., Ahmed, M. A. E., Schumann, C., Lepper, P. M., & Triantafilou, M. 2005b, "TLR8 and TLR7 are involved in the host's immune response to Human Parechovirus 1", Eur J Immunol 35, 2416-2423.
Publications
ORIGINAL PAPERS
(over 50 publications, only listed those since 2002)
1. Triantafilou, M. Miyake, K., Golenbock, D. T., and Triantafilou, K., (2002) Mediators of the innate immune recognition of bacteria concentrate in lipid rafts and facilitate lipopolysaccharide-induced cell activation J Cell Science 115, 2603-26011
2. Triantafilou, M., Brandenburg, K., Gutsmann, T., Seydel, U. and Triantafilou, K. (2002) Innate recognition of bacteria: engagement of multiple receptors. Critical Reviews in Immunology 22, 251-268
3. Triantafilou, M. and Triantafilou, K. (2003) Receptor cluster formation during activation by bacterial products J Endotox Res 9, 331-335
4. Triantafilou, K. and Triantafilou, M. (2003) Lipid raft microdomains: Key sites for Coxsackievirus A9 infectious cycle. Virology 317, 128-135
5. Triantafilou, M. and Triantafilou, K. (2004) Sepsis: molecular mechanisms underlying lipopolysaccharide recognition. Exp Rev Mol Medicine 2004, 1-18
6. Triantafilou, M., Brandenburg, K., Kusumoto, S., Fukase, K., Mackie, A., Seydel, U. and Triantafilou, K. (2004) Combinational clustering of receptors following stimulation by bacterial products determines LPS responses. Biochem J. 381, 527-36
7. Triantafilou, M., Morath, S., Mackie, A., Hartung, T. and Triantafilou, K. (2004) Lateral diffusion of Toll-like receptors reveals that they are transiently confined within lipid rafts on the plasma membrane. J Cell Science 117, 4007-4014
8. Triantafilou, K. and Triantafilou, M. (2004) Lipid raft dependent Coxsackievirus B4 internalization and rapid targeting to the Golgi. Virology 326, 6-19
9. Triantafilou, K and Triantafilou, M (2004) Coxsackievirus B4-induced inflammation in pancreatic cells is mediated through TLR4. J. Virology 78, 11313-11320
10. Orthopoulos, G., Triantafilou, K. and Triantafilou, M. (2004) Coxsackie B viruses use multiple receptors to infect human cardiac cells. J. Med. Virol. 74, 291-299
11. Triantafilou, M., Manukyan, M., Mackie, A., Morath, S., Hartung, T., Heine, H., and Triantafilou, K. (2004) Lipoteichoic acid and Toll-like receptor 2 internalization and targeting to the Golgi is lipid raft dependent. J. Biol. Chem 279, 40882-40889
12. Triantafilou, M. and Triantafilou, K. (2004) Heat shock protein 70 and heat shock protein 90 associate with Toll-like receptor 4 in response to bacterial lipopolysaccharide. Biochem. Soc. Trans. 32, 636-9
13. Lepper, P.M., Triantafilou, M., Schumann, C., Trautmann, M., Schneider, E.M. and Triantafilou, K. (2005) Lipopolysaccharides from Helicobacter pylori can act as antagonists for Toll-like receptor 4. Cellular Microbiol. 7, 519-28
14. Humphries, H.E., Triantafilou, M., Makepeace, B.L., Heckels, J.E., Triantafilou, K. and Christodoulides, M. (2005) Activation of human meningeal cells is modulated by LPS and non-LPS components of Neisseria meningitidis and is independent of toll-like receptor (TLR)2 and TLR4 signalling. Cell Microbiol. 7, 415-30.
15. Triantafilou, M. and Triantafilou, K. (2005) The dynamics of LPS recognition: complex orchestration of multiple receptors. J. Endotoxin Res 11, 5-11.
16. Manoukian, M., Triantafilou, K., Triantafilou, M., Mackie, A., Nilsen, N., Espevik, T., Wiesmueller, K.H., Ulmer, A.J., and Heine, H. (2005) Binding of lipopeptide to CD14 induces physical proximity of CD14, TLR2 and TLR1. Eur. J. Immunol. 35, 911-21.
17. Triantafilou, K., Orthopoulos, G., Vakakis, E., Ahmed, M.A.E., Golenbock, D.T., Lepper, P.M., and Triantafilou, M. (2005) Human cardiac inflammatory responses triggered by Coxsackie B Viruses are mainly Toll-like receptor (TLR) 8-dependent. Cellular Microbiol 7, 1117-1126
18. Triantafilou, K., Vakakis, E., Orthopoulos, G. Ahmed, M.A.E, Schumann, C., Lepper, P.M. and Triantafilou, M. (2005) TLR8 and TLR7 are involved in the host's immune response to Human Parechovirus 1. Eur J Immunol 35, 2416-2423
19. Schumann, C., Triantafilou, K., Kamenz, J., Hanke, H., Triantafilou, M., Witternman, S., Joos, T., Hombach, V., Schneider, E.M., and Lepper, P.M. (2006) Septic shock caused by Streptococcus pneumoniae in a post-splenectomy patient successfully treated with recombinant human activated protein C. Scand J. Infect Dis 38, 139-142
20. Schumann, C., Triantafilou, K., Maximillian Rasche, F., Moricke, A., Vogt, K., Triantafilou, M., Hahn, P., Schneider, E.M., and Lepper, P.M. (2006) Serum antibody positivity for distinct Helicobacter pylori antigens in benign and malignant gastroduodenal disease. Intern J Med Microbiol. 296: 223-8
21. Hajishengallins, G., Tapping, R.I., Harokopakis, E., Nishiyama, S., Ratti, P., Schifferle, R.E., Lyle, E.A., Triantafilou, M., Triantafilou, K., and Yoshimura, F. (2006) Differential interactions of fimbriae and lipopolysaccharide from Porphyromonas gingivalis with the Toll-like receptor 2-centered pattern recognition apparatus. Cellular Microbiol 8: 1557-70
22. Triantafilou, M., Gamper, F.G., Haston, R.M., Mouratis, M.A., Morath, S., Hartung, T. and Triantafilou, K.(2006) Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 heterodimers at the cell surface determines heterotypic associations with CD36 and intracellular targeting. J Biol. Chem. 281: 31002-11
23. Hajishengallins, G., Wang, M., Harokopakis, E., Triantafilou, M. and Triantafilou, K. (2006) Porphyromonas gingivalis fimbriae proactively modulate beta 2 integrin adhesive activity and promote binding and internalisation by macrophages. Infect Immun 74: 5658-66
24. Schumann, C., Triantafilou, K., Krueger, S., Hombach, V., Triantafilou, M., Becher, G., and Lepper, P.M. (2006) Detection of erythropoietin in exhaled breath condensate of nonhypoxic subjects using a multiplex bead array. Mediators Inflamm. 2006: 18061
25. Liang, S., Wang, M., Taping, R.I., Stepensky, V., Nawar, H.F., Triantafilou, M., Triantafilou, K., Connell, T.D. and Hajishengallins, G. (2007) Ganglioside GD1a is an essential coreceptor for Toll-like receptor 2 signaling in response to the B subunit of type IIb enterotoxin J Biol. Chem 282: 7532-42
26. Liang, S., Wang, M., Triantafilou, K., Triantafilou, M., Nawar, H.F., Russell, M.W., Connell, T.D., and Hajishengallins, G. (2007) The A subunit of type Iib enterotoxin (LT-IIb) suppresses the pro-inflammatory potential of the B subunit and its ability to recruit and interact with TLR2. J Immunol 178: 4811-9
27. Triantafilou, M., Gamper, F.G., Lepper, P.M., Mouratis, M.A., Schumann, C., Harokopakis, E., Schifferle, R.E., Hajishengallis, G., and Triantafilou, K. (2007) Lipopolysaccharides from atherosclerosis-associated bacteria antagonize TLR4, induce formation of TLR2/1/CD36 complexes in lipid rafts and trigger TLR2-induced inflammatory responses in human vascular endothelial cells. Cell. Microbiol. 9(8) 2030-9
28. Lepper, P.M., von Eynatten, M. Humpert, P.M., Triantafilou, M. and Triantafilou, K. (2007) Toll-like receptor polymorphisms and carotid artery intima-media thickness. Stroke 38(7):e50
29. Triantafilou, M., Uddin, A., Maher, S., Charalambous, N., Hamm, T.S.C., Alsumaiti, A., and Triantafilou, K. (2007) Bacillus anthracis lethal toxin evades Toll-like receptor (TLR) recognition, whereas its cell wall components trigger activation via TLR2/6 heterodimers Cellular Microbiol 9(12):2880-92
30. Lepper, P.M., Schumann, C., Triantafilou, K., Rasche, F.M., Schuster, T., Frank, H., Schneider, M.E., Triantafilou, M., and von Eynatten, M. (2007) Association of lipopolysaccharide binding protein and coronary artery disease in men. JACC 50(1):25-31
31. Triantafilou, M., Lepper, P.M., Briault, C.D., Ahmed, M.A., Dmochowski, J.M., Schumann, C. and Triantafilou, K. (2007) Chemokine receptor 4 (CXCR4) is part of the lipopolysaccharide "sensing apparatus". Eur J Immunol. 2008 Jan;38(1):192-203.
32. Parker, L.C., Prestwich, E.C., Ward, J.R., Smythe, E., Berry, A., Triantafilou, M., Triantafilou, K., Sabroe, I. (2008) A phosphatidylserine species inhibits a range of TLR- but not IL-1beta-induced inflammatory responses by disruption of membrane microdomains. J Immunol 181 (8), 5606-17
33. Triantafilou, M., Sawyer, D., Nor, A., Vakakis, E. and Triantafilou, K. (2008) Cell surface molecular chaperones as modulators of the innate immune response. Novartis Found Symp. 2008;291:74-9
34. Hajishengallis, G., Wang, M., Liang, S., Triantafilou, M., Triantafilou, K. (2008) Pathogen induction of CXCR4/TLR2 crosstalk impairs host function. Proc Natl Acad Sci U S A. 9;105(36):13532-7