TLR- and CXCR1-dependent innate immunity: insights into the genetics of urinary tract infections.

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TLR- and CXCR1-dependent innate immunity: insights into the genetics of urinary tract infections. / Ragnarsdottir, Bryndis; Fischer, Hans; Godaly, Gabriela; Grönberg Hernandez, Jenny; Gustafsson, Mattias; Karpman, Diana; Lundstedt, Ann-Charlotte; Lutay, Nataliya; Rämisch, S; Svensson, M L; Wullt, Björn; Yadav, Manisha; Svanborg, Catharina.

I: European Journal of Clinical Investigation, Vol. 38 Suppl 2, 2008, s. 12-20.

Forskningsoutput: TidskriftsbidragÖversiktsartikel

Harvard

Ragnarsdottir, B, Fischer, H, Godaly, G, Grönberg Hernandez, J, Gustafsson, M, Karpman, D, Lundstedt, A-C, Lutay, N, Rämisch, S, Svensson, ML, Wullt, B, Yadav, M & Svanborg, C 2008, 'TLR- and CXCR1-dependent innate immunity: insights into the genetics of urinary tract infections.', European Journal of Clinical Investigation, vol. 38 Suppl 2, s. 12-20. https://doi.org/10.1111/j.1365-2362.2008.02004.x

APA

Ragnarsdottir, B., Fischer, H., Godaly, G., Grönberg Hernandez, J., Gustafsson, M., Karpman, D., Lundstedt, A-C., Lutay, N., Rämisch, S., Svensson, M. L., Wullt, B., Yadav, M., & Svanborg, C. (2008). TLR- and CXCR1-dependent innate immunity: insights into the genetics of urinary tract infections. European Journal of Clinical Investigation, 38 Suppl 2, 12-20. https://doi.org/10.1111/j.1365-2362.2008.02004.x

CBE

Ragnarsdottir B, Fischer H, Godaly G, Grönberg Hernandez J, Gustafsson M, Karpman D, Lundstedt A-C, Lutay N, Rämisch S, Svensson ML, Wullt B, Yadav M, Svanborg C. 2008. TLR- and CXCR1-dependent innate immunity: insights into the genetics of urinary tract infections. European Journal of Clinical Investigation. 38 Suppl 2:12-20. https://doi.org/10.1111/j.1365-2362.2008.02004.x

MLA

Vancouver

Author

Ragnarsdottir, Bryndis ; Fischer, Hans ; Godaly, Gabriela ; Grönberg Hernandez, Jenny ; Gustafsson, Mattias ; Karpman, Diana ; Lundstedt, Ann-Charlotte ; Lutay, Nataliya ; Rämisch, S ; Svensson, M L ; Wullt, Björn ; Yadav, Manisha ; Svanborg, Catharina. / TLR- and CXCR1-dependent innate immunity: insights into the genetics of urinary tract infections. I: European Journal of Clinical Investigation. 2008 ; Vol. 38 Suppl 2. s. 12-20.

RIS

TY - JOUR

T1 - TLR- and CXCR1-dependent innate immunity: insights into the genetics of urinary tract infections.

AU - Ragnarsdottir, Bryndis

AU - Fischer, Hans

AU - Godaly, Gabriela

AU - Grönberg Hernandez, Jenny

AU - Gustafsson, Mattias

AU - Karpman, Diana

AU - Lundstedt, Ann-Charlotte

AU - Lutay, Nataliya

AU - Rämisch, S

AU - Svensson, M L

AU - Wullt, Björn

AU - Yadav, Manisha

AU - Svanborg, Catharina

PY - 2008

Y1 - 2008

N2 - The susceptibility to urinary tract infection (UTI) is controlled by the innate immune response and Toll like receptors (TLRs) are the sentinels of this response. If productive, TLR4 signalling may initiate the symptomatic disease process. In the absence of TLR4 signalling the infected host instead develops an asymptomatic carrier state. The activation of mucosal TLR4 is also influenced by the properties of the infecting strain, and pathogens use their virulence factors to trigger 'pathogen-specific' TLR4 responses in the urinary tract but do not respond to the asymptomatic carrier strains in patients with asymptomatic bacteriuria (ABU). The TLR4 dependence has been demonstrated in mice and the relevance of low TLR4 function for protection for human disease was recently confirmed in children with asymptomatic bacteriuria, who expressed less TLR4 than age matched controls. Functional chemokines and functional chemokine receptors are crucial for neutrophil recruitment, and for the neutrophil dependent bacterial clearance. Interleukin (IL)-8 receptor deficient mice develop acute septic infections and chronic tissue damage, due to aberrant neutrophil function. This mechanism is relevant for human UTI as pyelonephritis prone children express low levels of the human CXCL8 (Il-8) receptor, CXC chemokine receptor 1 (CXCR1) and often have heterozygous CXCR1 polymorphisms. This review illustrates how intimately the innate response and the susceptibility to UTI are linked and sophisticated recognition mechanisms that rely on microbial virulence and on host TLR4 and CXCR1 signalling.

AB - The susceptibility to urinary tract infection (UTI) is controlled by the innate immune response and Toll like receptors (TLRs) are the sentinels of this response. If productive, TLR4 signalling may initiate the symptomatic disease process. In the absence of TLR4 signalling the infected host instead develops an asymptomatic carrier state. The activation of mucosal TLR4 is also influenced by the properties of the infecting strain, and pathogens use their virulence factors to trigger 'pathogen-specific' TLR4 responses in the urinary tract but do not respond to the asymptomatic carrier strains in patients with asymptomatic bacteriuria (ABU). The TLR4 dependence has been demonstrated in mice and the relevance of low TLR4 function for protection for human disease was recently confirmed in children with asymptomatic bacteriuria, who expressed less TLR4 than age matched controls. Functional chemokines and functional chemokine receptors are crucial for neutrophil recruitment, and for the neutrophil dependent bacterial clearance. Interleukin (IL)-8 receptor deficient mice develop acute septic infections and chronic tissue damage, due to aberrant neutrophil function. This mechanism is relevant for human UTI as pyelonephritis prone children express low levels of the human CXCL8 (Il-8) receptor, CXC chemokine receptor 1 (CXCR1) and often have heterozygous CXCR1 polymorphisms. This review illustrates how intimately the innate response and the susceptibility to UTI are linked and sophisticated recognition mechanisms that rely on microbial virulence and on host TLR4 and CXCR1 signalling.

U2 - 10.1111/j.1365-2362.2008.02004.x

DO - 10.1111/j.1365-2362.2008.02004.x

M3 - Review article

C2 - 18826477

VL - 38 Suppl 2

SP - 12

EP - 20

JO - European Journal of Clinical Investigation

JF - European Journal of Clinical Investigation

SN - 0014-2972

ER -