Induction of indoleamine 2,3-dioxygenase by uropathogenic bacteria attenuates innate responses to epithelial infection

Jennifer A. Loughman, David A. Hunstad

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1830-1839
Number of pages10
JournalJournal of Infectious Diseases
Volume205
Issue number12
DOIs
StatePublished - Jun 15 2012

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