Susceptibility to acute pyelonephritis or asymptomatic bacteriuria: host-pathogen interaction in urinary tract infections.
Our knowledge of the molecular mechanisms of urinary tract infection (UTI) pathogenesis has advanced greatly in recent years. In this review, we provide a general background of UTI pathogenesis, followed by an update on the mechanisms of UTI susceptibility, with a particular focus on genetic variation affecting innate immunity. The innate immune response of the host is critically important in the antibacterial defence mechanisms of the urinary tract, and bacterial clearance normally proceeds without sequelae. However, slight dysfunctions in these mechanisms may result in acute disease and tissue destruction. The symptoms of acute pyelonephritis are caused by the innate immune response, and inflammation in the urinary tract decreases renal tubular function and may give rise to renal scarring, especially in paediatric patients. In contrast, in children with asymptomatic bacteriuria (ABU), bacteria persist without causing symptoms or pathology. Pathogenic agents trigger a response determined by their virulence factors, mediating adherence to the urinary tract mucosa, signalling through Toll-like receptors (TLRs) and activating the defence mechanisms. In ABU strains, such virulence factors are mostly not expressed. However, the influence of the host on UTI severity cannot be overestimated, and rapid progress is being made in clarifying host susceptibility mechanisms. For example, genetic alterations that reduce TLR4 function are associated with ABU, while polymorphisms reducing IRF3 or CXCR1 expression are associated with acute pyelonephritis and an increased risk for renal scarring. It should be plausible to "individualize" diagnosis and therapy by combining information on bacterial virulence and the host response.
Institute of Laboratory Medicine, Section of Microbiology, Immunology and Glycobiology (MIG), Lund University, Sölvegatan 23, 22362, Lund, Sweden.
Bryndís
B
Ragnarsdóttir
Institute of Laboratory Medicine, Section of Microbiology, Immunology and Glycobiology (MIG), Lund University, Sölvegatan 23, 22362, Lund, Sweden. Catharina.Svanborg@med.lu.se.
Catharina
C
Svanborg
D000208:Acute Disease; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D058070:Asymptomatic Diseases; D001419:Bacteria / Q000187:drug effects / Q000276:immunology / Q000472:pathogenicity*; D001437:Bacteriuria / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000382:microbiology*; D024881:Drug Resistance, Bacterial; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D040941:Heredity; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D010641:Phenotype; D011379:Prognosis; D011704:Pyelonephritis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000382:microbiology*; D012307:Risk Factors; D014552:Urinary Tract Infections / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000382:microbiology*; D014774:Virulence
D000900:Anti-Bacterial Agents