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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Vydáno v:	Scientific reports Ročník 9; číslo 1; s. 106
Hlavní autoři:	Emal, Diba, Rampanelli, Elena, Claessen, Nike, Bemelman, Frederike J., Leemans, Jaklien C., Florquin, Sandrine, Dessing, Mark C.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 14.01.2019 Nature Publishing Group
Témata:	13 13/1 13/31 13/51 38/77 631/250/255/1318 631/80/304 82/80 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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Popis
Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-018-37482-x