Interleukin 8 receptor deficiency confers susceptibility to acute experimental pyelonephritis and may have a human counterpart

Research output: Contribution to journalArticle

Standard

Interleukin 8 receptor deficiency confers susceptibility to acute experimental pyelonephritis and may have a human counterpart. / Frendeus, Björn; Godaly, Gabriela; Hang, Long; Karpman, Diana; Lundstedt, Ann-Charlotte; Svanborg, Catharina.

In: Journal of Experimental Medicine, Vol. 192, No. 6, 2000, p. 881-890.

Research output: Contribution to journalArticle

Harvard

APA

CBE

MLA

Vancouver

Author

RIS

TY - JOUR

T1 - Interleukin 8 receptor deficiency confers susceptibility to acute experimental pyelonephritis and may have a human counterpart

AU - Frendeus, Björn

AU - Godaly, Gabriela

AU - Hang, Long

AU - Karpman, Diana

AU - Lundstedt, Ann-Charlotte

AU - Svanborg, Catharina

PY - 2000

Y1 - 2000

N2 - Neutrophils migrate to infected mucosal sites that they protect against invading pathogens. Their interaction with the epithelial barrier is controlled by CXC chemokines and by their receptors. This study examined the change in susceptibility to urinary tract infection (UTI) after deletion of the murine interleukin 8 receptor homologue (mIL-8Rh). Experimental UTIs in control mice stimulated an epithelial chemokine response and increased chemokine receptor expression. Neutrophils migrated through the tissues to the epithelial barrier that they crossed into the lumen, and the mice developed pyuria. In mIL-8Rh knockout (KO) mice, the chemokine response was intact, but the epithelial cells failed to express IL-8R, and neutrophils accumulated in the tissues. The KO mice were unable to clear bacteria from kidneys and bladders and developed bacteremia and symptoms of systemic disease, but control mice were fully resistant to infection. The experimental UTI model demonstrated that IL-8R-dependent mechanisms control the urinary tract defense, and that neutrophils are essential host effector cells. Patients prone to acute pyelonephritis also showed low CXC chemokine receptor 1 expression compared with age-matched controls, suggesting that chemokine receptor expression may also influence the susceptibility to UTIs in humans. The results provide a first molecular clue to disease susceptibility of patients prone to acute pyelonephritis.

AB - Neutrophils migrate to infected mucosal sites that they protect against invading pathogens. Their interaction with the epithelial barrier is controlled by CXC chemokines and by their receptors. This study examined the change in susceptibility to urinary tract infection (UTI) after deletion of the murine interleukin 8 receptor homologue (mIL-8Rh). Experimental UTIs in control mice stimulated an epithelial chemokine response and increased chemokine receptor expression. Neutrophils migrated through the tissues to the epithelial barrier that they crossed into the lumen, and the mice developed pyuria. In mIL-8Rh knockout (KO) mice, the chemokine response was intact, but the epithelial cells failed to express IL-8R, and neutrophils accumulated in the tissues. The KO mice were unable to clear bacteria from kidneys and bladders and developed bacteremia and symptoms of systemic disease, but control mice were fully resistant to infection. The experimental UTI model demonstrated that IL-8R-dependent mechanisms control the urinary tract defense, and that neutrophils are essential host effector cells. Patients prone to acute pyelonephritis also showed low CXC chemokine receptor 1 expression compared with age-matched controls, suggesting that chemokine receptor expression may also influence the susceptibility to UTIs in humans. The results provide a first molecular clue to disease susceptibility of patients prone to acute pyelonephritis.

KW - chemokine receptor

KW - urinary tract infection

KW - knockout mice

KW - mucosal immunity

KW - lipopolysaccharide

M3 - Article

VL - 192

SP - 881

EP - 890

JO - Journal of Experimental Medicine

T2 - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 1540-9538

IS - 6

ER -