Pyelonephritic Escherichia coli Expressing P Fimbriae Decrease Immune Response of the Mouse Kidney

Abstract

P fimbriae are proteinaceous appendages on the surface of Escherichia coli bacteria that mediate adherence to uroepithelial cells. E. coli that express P fimbriae account for the majority of ascending urinary tract infections in women with normal urinary tracts. The hypothesis that P fimbriae on uropathic E. coli attach to renal epithelia and may regulate the immune response to establish infection was investigated. The polymeric Ig receptor (pIgR), produced by renal epithelia, transports IgA into the urinary space. Kidney pIgR and urine IgA levels were analyzed in a mouse model of ascending pyelonephritis, using E. coli with (P؉) and without (P؊) P fimbriae, to determine whether P(؉) E. coli regulate epithelial pIgR expression and IgA transport into the urine. (P؉) E. coli establish infection and persist to a greater amount than P(؊) E. coli. P(؉)-infected mice downregulate pIgR mRNA and protein levels compared with P(؊)-infected or PBS controls at >48 h. The decrease in pIgR was associated with decreased urinary IgA levels in the P(؉)-infected group at 48 h. pIgR mRNA and protein also decline in P(؉) E. coli-infected LPS-hyporesponsive mice. These studies identify a novel virulence mechanism of E. coli that express P fimbriae. It is proposed that P fimbriae decrease pIgR expression in the kidney and consequently decrease IgA transport into the urinary space. This may explain, in part, how E. coli that bear P fimbriae exploit the immune system of human hosts to establish ascending pyelonephritis. Escherichia coli that express P fimbriae are the most common cause for upper urinary tract infections (UTI) or pyelonephritis (1). The P fimbriae mediate adherence to uroepithelial cells by binding to the Gal␣(1 to 4)Gal disaccharide on the apical surface of renal epithelial cells, glomeruli, and endothelia (2). The expression of P fimbriae on E. coli is important in establishing pyelonephritis, as P fimbriae-specific antibodies prevent the adherence of bacteria to uroepithelial cells in vitro (3) and protect animals from ascending E. coli pyelonephritis in vivo (4). Although P fimbriae are not the sole virulence factor on uropathic E. coli, pyelonephritis with P(ϩ) E. coli strains are more often associated with kidney histopathology than P(Ϫ) E. coli (5). In addition to its role as an adhesin, E. coli that express P fimbriae may determine the pattern of the local immune response via interaction with its P-specific glycosphingolipid receptors present on uroepithelial cells (6) and/or by signaling via inflammatory cytokines (7).The secretions that protect the mucosal surface of renal epithelia contain an array of host defense factors, including secretory immunoglobulins, of which IgA is the major class. The polymeric Ig receptor (pIgR) is responsible for transporting these secretory immunoglobulins (S-Ig) in vesicles from the basolateral to the apical surface of epithelial cells (8 -10), including renal tubule cells. The extracellular portion of the pIgR, termed secretory component (SC), is cleaved at the apical surface ...

Impact of Toll-like receptor signalling on urinary tract infection

“…Bladder epithelial cells can be activated by type 1 pilated E. coli via TLR4 to produce inflammatory mediators, e.g. IL-6 and IL-8, as well as chemokines and antimicrobial peptides (defensins) [2,8]. It remains controversial whether or not mCD14, a pleiotropic endotoxin receptor, or soluble CD14 (sCD14) are necessary as co-stimulating factors [18,19]: in most studies, bladder mucosal cells and kidney epithelial cells do not express mCD14 [22,23].…”

“…During recent years, a panel of virulence factors of pyelonephritic bacteria became apparent, e.g. adherence factors, cytotoxins, the potency to downregulate mucosa-protective secretory immunoglobulin A (IgA) (polymeric immunoglobulin receptor) in kidney cells and deficiency of IgG subclasses [1,2]. Persistence of bacterial antigen in the renal tissue (mainly interstitium) might be an additional factor in the pathogenesis of chronic bacterial nephritis [3][4][5][6], clinically defined by lowcount bacteriuria, tubular proteinuria, impaired concentration ability, elevated cystatin C serum levels and typical signs as assessed by ultrasound and intravenous urography [3][4][5][6][7].…”

Cranberry products in the prevention of urinary tract infections: examining the evidence

“…More virulent E. coli causing pyelonephritis and complicated UTI typically bear p-fimbriae in addition to type-1 fimbriae. Adhesion of p-fimbriated E. coli with their specific lectins [9][10][11] is not inhibitable by fructose or other low molecular carbohydrates (hence mannose-resistant fimbriae).…”

Cranberry juice – a well-characterized folk-remedy against bacterial urinary tract infection

“…The more vicious E. coli isolates from patients with pyelonephritis and recurrent UTI, bear further types of fimbriae, notably p-fimbriae. P-fimbriae are associated with the alphaGal [1][2][3][4] beta-Gal specific lectin, a marker of pathogenicity. The prefix "p" is derived from pyelonephritis, and binding of p-fimbriated E. coli to glycosphingolipids of the lipid-double-membrane of renal cells precedes renal parenchymal invasion.…”

“…The prefix "p" is derived from pyelonephritis, and binding of p-fimbriated E. coli to glycosphingolipids of the lipid-double-membrane of renal cells precedes renal parenchymal invasion. P-fimbriated E. coli overrun the kidney's immunological defense lines by impairing synthesis and secretion of urinary IgA through inhibition of the polymeric Ig-Receptor on renal epithelia [2]. Adhesion mediated by p-fimbriae is not inhibitable by fructose or other low-molecular carbohydrates (hence mannoseresistent fimbriae).…”