Microbial activation of mucosal inflammation
Introduction
Most infectious agents first meet their hosts at mucosal sites. Upon contact, when bacteria attach to epithelial cell receptors, a "cross-talk" is initiated, and both bacteria and host respond and are modified as a result of this encounter. Highly specific signalling pathways are activated by individual bacterial virulence factors, leading to a response repertoire characteristic for each pathogen.Cell activation causes mucosal inflammation, which explains many aspects of disease in the patient. We study the molecular mechanisms of mucosal cell activation with focus on human urinary epithelial cells and uropathogenic Escherichia coli. This is one example of protein- carbohydrate interaction, where bacterial proteins associated with surface fimbriae bind with high specificity to oligosaccharide epitopes in cell surface glycolipids or glycoproteins. We study how the binding causes cell activation. This group is headed by Hans Fischer.
Group members
| Fischer, Hans | Docent | hans.fischer@med.lu.se | 046-2227017 |
| Grönberg Hernandez, Jenny | PhD Student | jenny.gronberg_hernandez@med.lu.se | 046-2223292 |
| Lutay, Nataliya | Postdoc | nataliya.lutay@med.lu.se | 046-2227017 |
| Ragnarsdottir, Bryndis | PhD Student | bryndis.ragnarsdottir@med.lu.se | 046-2223292 |
| Svanborg, Catharina* | Professor | Catharina.Svanborg@med.lu.se | 046-2227185 |
| Svensson, Majlis | Postdoc | majlis.svensson@med.lu.se | 046-173233 |
| Yadav, Manisha | Postdoc | manisha.yadav@med.lu.se | 046-2229262 |
Recent articles
| Authors | Title | Journal | Pubmed link |
| Cirl C, Wieser A, Yadav M, Duerr S, Schubert S, Fischer H, Stappert D, Wantia N, Rodriguez N, Wagner H, Svanborg C, Miethke T. | Subversion of Toll-like receptor signaling by a unique family of bacterial Toll/interleukin-1 receptor domain-containing proteins. | Nat Med. 2008 Mar 9 | Pubmed: 18327267 |
| Zdziarski J, Svanborg C, Wullt B, Hacker J, Dobrindt U. | Molecular basis of commensalism in the urinary tract: low virulence or virulence attenuation? | Infect Immun. 2007 Nov 26 | Pubmed: 18039831 |
| Lundstedt AC, McCarthy S, Gustafsson MC, Godaly G, Jodal U, Karpman D, Leijonhufvud I, Linden C, Martinell J, Ragnarsdottir B, Samuelsson M, Truedsson L, Andersson B, Svanborg C. | A genetic basis of susceptibility to acute pyelonephritis. | PLoS ONE. 2007 Sep 5;2(9) | Pubmed: 17786197 |
| Ragnarsdottir B, Samuelsson M, Gustafsson MC, Leijonhufvud I, Karpman D, Svanborg C. | Reduced toll-like receptor 4 expression in children with asymptomatic bacteriuria. | J Infect Dis. 2007 Aug 1;196(3):475-84. | Pubmed: 17597463 |
| Godaly G, Svanborg C. | Urinary tract infections revisited. | Kidney Int. 2007 Apr;71(8):721-3. | Pubmed: 17429419 |
| Bergsten G, Wullt B, Schembri MA, Leijonhufvud I, Svanborg C. | Do type 1 fimbriae promote inflammation in the human urinary tract? | Cell Microbiol. 2007 Jul;9(7):1766-81. | Pubmed: 17359236 |
| Lundstedt AC, Leijonhufvud I, Ragnarsdottir B, Karpman D, Andersson B, Svanborg C. | Inherited susceptibility to acute pyelonephritis: a family study of urinary tract infection. | J Infect Dis. 2007 Apr 15;195(8):1227-34. | Pubmed: 17357062 |
| Godaly G, Otto G, Burdick MD, Strieter RM, Svanborg C. | Fimbrial lectins influence the chemokine repertoire in the urinary tract mucosa. | Kidney Int. 2007 Apr;71(8):778-86. | Pubmed: 17228365 |
| Fischer H, Ellstrom P, Ekstrom K, Gustafsson L, Gustafsson M, Svanborg C. | Ceramide as a TLR4 agonist; a putative signalling intermediate between sphingolipid receptors for microbial ligands and TLR4. | Cell Microbiol. 2007 May;9(5):1239-51. | Pubmed: 17223929 |
| Holmqvist B, Olsson CF, Svensson ML, Svanborg C, Forsell J, Alm P. | Expression of nitric oxide synthase isoforms in the mouse kidney: cellular localization and influence by lipopolysaccharide and Toll-like receptor 4. | J Mol Histol. 2005 Oct;36(8-9):499-516. | Pubmed: 16733795 |
| Svensson M, Platt FM, Svanborg C. | Glycolipid receptor depletion as an approach to specific antimicrobial therapy. | FEMS Microbiol Lett. 2006 May;258(1):1-8. | Pubmed: 16630247 |
| Stahl AL, Svensson M, Morgelin M, Svanborg C, Tarr PI, Mooney JC, Watkins SL, Johnson R, Karpman D. | Lipopolysaccharide from enterohemorrhagic Escherichia coli binds to platelets through TLR4 and CD62 and is detected on circulating platelets in patients with hemolytic uremic syndrome. | Blood. 2006 Jul 1;108(1):167-76. | Pubmed: 16514062 |
| Svanborg C, Bergsten G, Fischer H, Godaly G, Gustafsson M, Karpman D, Lundstedt AC, Ragnarsdottir B, Svensson M, Wullt B. | Uropathogenic Escherichia coli as a model of host-parasite interaction. | Curr Opin Microbiol. 2006 Feb;9(1):33-9. | Pubmed: 16406777 |
| Fischer H, Yamamoto M, Akira S, Beutler B, Svanborg C. | Mechanism of pathogen-specific TLR4 activation in the mucosa: fimbriae, recognition receptors and adaptor protein selection. | Eur J Immunol. 2006 Feb;36(2):267-77. | Pubmed: 16385628 |
| Bergsten G, Wullt B, Svanborg C. | Escherichia coli, fimbriae, bacterial persistence and host response induction in the human urinary tract. | Int J Med Microbiol. 2005 Oct;295(6-7):487-502. | Pubmed: 16238023 |
| Svensson M, Irjala H, Alm P, Holmqvist B, Lundstedt AC, Svanborg C. | Natural history of renal scarring in susceptible mIL-8Rh-/- mice. | Kidney Int. 2005 Jan;67(1):103-10. | Pubmed: 15610233 |
| Samuelsson P, Hang L, Wullt B, Irjala H, Svanborg C | Toll-like receptor 4 expression and cytokine responses in the human urinary tract mucosa. | Infect Immun. 2004 Jun;72(6):3179-86. | Pubmed: 15155619 |
| Bergsten G, Samuelsson M, Wullt B, Leijonhufvud I, Fischer H, Svanborg C. | PapG-dependent adherence breaks mucosal inertia and triggers the innate host response. | J Infect Dis. 2004 May 1;189(9):1734-42. | Pubmed: 15116313 |
| Wullt B, Bergsten G, Fischer H, Godaly G, Karpman D, Leijonhufvud I, Lundstedt AC, Samuelsson P, Samuelsson M, Svensson ML, Svanborg C. | The host response to urinary tract infection. | Infect Dis Clin North Am. 2003 Jun;17(2):279-301. | Pubmed: 12848471 |
| Wullt B, Bergsten G, Samuelsson M, Svanborg C. | Effect of P fimbriae on pyuria and bacterial colonization of the human urinary tract | Urologe A. 2003 Feb;42(2):233-7 | Pubmed: 12607092 |
| Svensson M, Frendeus B, Butters T, Platt F, Dwek R, Svanborg C. | Glycolipid depletion in antimicrobial therapy. | Mol Microbiol. 2003 Jan;47(2):453-61. | Pubmed: 12519195 |