Subversion of Host Innate Immunity by Uropathogenic Escherichia coli

Abstract

Uropathogenic Escherichia coli (UPEC) cause the majority of community-onset urinary tract infections (UTI) and represent a major etiologic agent of healthcare-associated UTI. Introduction of UPEC into the mammalian urinary tract evokes a well-described inflammatory response, comprising pro-inflammatory cytokines and chemokines as well as cellular elements (neutrophils and macrophages). In human UTI, this inflammatory response contributes to symptomatology and provides means for diagnosis by standard clinical testing. Early in acute cystitis, as demonstrated in murine models, UPEC gains access to an intracellular niche that protects a population of replicating bacteria from arriving phagocytes. To ensure the establishment of this protected niche, UPEC employ multiple strategies to attenuate and delay the initiation of host inflammatory components, including epithelial secretion of chemoattractants. Recent work has also revealed novel mechanisms by which UPEC blunts neutrophil migration across infected uroepithelium. Taken together, these attributes distinguish UPEC from commensal and nonpathogenic E. coli strains. This review highlights the unique immune evasion and suppression strategies of this bacterial pathogen and offers directions for further study; molecular understanding of these mechanisms will inform the development of adjunctive, anti-virulence therapeutics for UTI.

Keywords: cystitis; effectors; filamentation; immune evasion; intracellular bacterial communities; neutrophils; urinary tract infection.

Figure 1

Intracellular UPEC communities are protected from neutrophil attack. Confocal microscopy of a C57BL/6J female mouse bladder harvested during acute cystitis (16 h post infection), viewed from a luminal perspective, shows an intracellular bacterial community of UPEC (yellow) within a binucleate superficial facet cell that is surrounded by recruited neutrophils (revealed by red nuclear staining; larger, round epithelial cell nuclei are also visible). UPEC strain UTI89 expressing green fluorescent protein (GFP) was used for infection, and bladder was fixed and stained with Syto 61 red nuclear stain [41].

Figure 2

Filamentous UPEC resist phagocytosis in the bladder. Confocal microscopy of a C57BL/6J female mouse harvested 24 h post-infection shows a surface (luminal) collection of bacillary and filamentous GFP-expressing UPEC strain UTI89 (green) in which the bacterial filaments are heavily intermingled with neutrophils (red nuclei, as in Figure 1). Scale bar, 10 μm.