Calcineurin inhibitor Tacrolimus impairs host immune response against urinary tract infection

Calcineurin inhibitor Tacrolimus, is a potent immunosuppressive drug widely used in order to prevent acute graft rejection. Urinary tract infection (UTI) is the most frequent infectious complication in renal transplant patients and long-term use of Tacrolimus might be involved in higher susceptibili...

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Bibliographic Details
Published in:Scientific reports Vol. 9; no. 1; p. 106
Main Authors: Emal, Diba, Rampanelli, Elena, Claessen, Nike, Bemelman, Frederike J., Leemans, Jaklien C., Florquin, Sandrine, Dessing, Mark C.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 14.01.2019
Nature Publishing Group
Subjects:
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Activating transcription factor 3
Animals
Bacteremia
Bacterial diseases
Bacterial infections
Bacterial Load
Calcineurin
Calcineurin inhibitors
Calcineurin Inhibitors - administration & dosage
Calcineurin Inhibitors - adverse effects
CXCR2 protein
Cystitis
Disease Models, Animal
E coli
Escherichia coli Infections - immunology
Escherichia coli Infections - pathology
Female
Graft rejection
Granulocytes
Granulocytes - drug effects
Granulocytes - immunology
Humanities and Social Sciences
Immune response
Immunologic Factors - metabolism
Immunosuppressive agents
Immunosuppressive Agents - administration & dosage
Immunosuppressive Agents - adverse effects
Innate immunity
Inoculation
Kidney transplantation
Leukocytes (granulocytic)
Macrophages
Mice
multidisciplinary
Peroxidase - metabolism
Phagocytosis - drug effects
Pyelonephritis
Rodents
Science
Science (multidisciplinary)
Tacrolimus
Tacrolimus - administration & dosage
Tacrolimus - adverse effects
TLR5 protein
Toll-like receptors
Urinary tract
Urinary tract diseases
Urinary tract infections
Urinary Tract Infections - immunology
Urinary Tract Infections - pathology
Urogenital system
Uropathogenic Escherichia coli - growth & development
Uropathogenic Escherichia coli - immunology
ISSN:2045-2322, 2045-2322
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Summary:Calcineurin inhibitor Tacrolimus, is a potent immunosuppressive drug widely used in order to prevent acute graft rejection. Urinary tract infection (UTI) is the most frequent infectious complication in renal transplant patients and long-term use of Tacrolimus might be involved in higher susceptibility to bacterial infections. It remains largely unknown how Tacrolimus affects the host innate immune response against lower and upper UTI. To address this issue, we used experimental UTI model by intravesical inoculation of uropathogenic E . coli in female wild-type mice pre-treated with Tacrolimus or solvent (CTR). We found that Tacrolimus pre-treated mice displayed higher bacterial loads (cystitis, pyelonephritis and bacteremia) than CTR mice. Granulocytes from Tacrolimus pre-treated mice phagocytized less E . coli , released less MPO and expressed decreased levels of CXCR2 receptor upon infection. Moreover, Tacrolimus reduced TLR5 expression in bladder macrophages during UTI. This immunosuppressive state can be explained by the upregulation of TLR-signaling negative regulators (A20, ATF3, IRAK-M and SOCS1) and parallel downregulation of TLR5 as observed in Tacrolimus treated granulocytes and macrophages. We conclude that Tacrolimus impairs host innate immune responses against UTI.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-37482-x