Induction of Indoleamine 2,3-Dioxygenase by Uropathogenic Bacteria Attenuates Innate Responses to Epithelial Infection

Uropathogenic Escherichia coli (UPEC) are the chief cause of urinary tract infections. Although neutrophilic inflammation is a hallmark of disease, previous data indicate that UPEC promotes local dampening of host innate immune responses. Here, we show that UPEC attenuates innate responses to epithe...

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Bibliographic Details
Published in:The Journal of infectious diseases 2012-06, Vol.205 (12), p.1830-1839
Main Authors: Loughman, Jennifer A., Hunstad, David A.
Format: Article
Language:English
Subjects:
Animals
Bacteria
Bacteriology
Biological and medical sciences
Cystitis
Cystitis - immunology
Cystitis - microbiology
Disease Models, Animal
Epithelial cells
Epithelial Cells - enzymology
Epithelial Cells - immunology
Epithelial Cells - microbiology
Fundamental and applied biological sciences. Psychology
Host-Pathogen Interactions
Humans
Immune Evasion
Immunity, Innate
Indoleamine-Pyrrole 2,3,-Dioxygenase - deficiency
Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism
Infections
Infectious diseases
Interferons
Major and Brief Reports
Medical sciences
Mice
Mice, Inbred C57BL
Microbial Viability
Microbiology
Miscellaneous
Neutrophils
Neutrophils - immunology
Neutrophils - microbiology
Polymerase chain reaction
Urinary bladder
Uropathogenic Escherichia coli
Uropathogenic Escherichia coli - immunology
Uropathogenic Escherichia coli - pathogenicity
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Summary:Uropathogenic Escherichia coli (UPEC) are the chief cause of urinary tract infections. Although neutrophilic inflammation is a hallmark of disease, previous data indicate that UPEC promotes local dampening of host innate immune responses. Here, we show that UPEC attenuates innate responses to epithelial infection by inducing expression of indoleamine 2,3-dioxygenase (IDO), a host enzyme with previously defined roles in adaptive immune regulation. UPEC induced IDO expression in human uroepithelial cells and polymorphonuclear leukocytes (PMN) in vitro and in bladder tissue during murine cystitis via a noncanonical, interferon-independent pathway. In the bladders of UPEC-infected IDO-deficient mice, we observed augmented expression of proinflammatory cytokines and local inflammation, correlated with reduced survival of extracellular bacteria. Pharmacologic inhibition of IDO also increased human PMN transepithelial migration. Stimulation of IDO expression therefore represents a pathogen strategy to create local immune privilege at epithelial surfaces, attenuating innate responses to promote colonization and the establishment of infection.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jis280