The inflammatory response to Gram-negative infection was studied in LPS responder and nonresponder C3H mice. Twenty-four hours after ascending E. coli urinary tract infection, an influx of neutrophils into the urine was observed in C3H/HeN mice (Lpsn,Lpsn); no significant neutrophil influx occurred in C3H/HeJ mice (Lpsd,Lpsd) at this time. A second peak of urinary neutrophil excretion was observed in both strains of mice approximately 6 days post-infection. The first, but not the second peak was inducible by inoculation with formalin-killed E. coli but not by Gram-positive bacteria. This finding suggested that the first peak is triggered by LPS, whereas the second peak emanates from other bacterial components which activate both LPS responder and nonresponder mice. The first peak of the inflammatory response was inversely related to bacterial clearance. C3H/HeJ mice (Lpsd,Lpsd) retained about 2000-fold more E. coli in the kidneys than C3H/HeN mice (Lpsn,Lpsn). The infection persisted despite the late-occurring influx of neutrophils in C3H/HeJ mice. These results suggest that an inflammatory response to LPS is required for the elimination of a local Gram-negative infection.

Animals↗

PubMed1987

Bacterial virulence in urinary tract infection.

The severity of an infection is a function of the resistance of the host and the virulence of the infecting strain. Infections of the urinary tract can be caused by a wide range of gram-negative and gram-positive bacteria, which also are constituents of the normal flora. Indeed, most uropathogens originate from the intestinal tract. Still, the virulence concept implies that bacteria associated with urinary tract infections differ from members of the indigenous flora not causing infections. This review attempts to summarize the mechanisms known to contribute to bacterial virulence in the urinary tract and their relevance in different patient groups.

Adult↗

PubMed1986

Antibodies to Escherichia coli and anti-adhesive activity in paired serum, hepatic and gall bladder bile samples.

Human bile contains a mixture of immunoglobulins excreted through the liver and produced in the biliary tract. This study examines the specific antibody activity of the biliary immunoglobulins against Escherichia coli antigens. Paired samples of serum, hepatic bile, and gall bladder bile were obtained from 23 patients with gallstones and five patients with healthy gall bladders. Antibody activity against E. coli antigens was found in all the sera and most of the bile samples. The levels of IgA, IgM, IgG, and secretory component (SC)-combined antibodies were lower in bile than in serum. Selective treatment of IgA by the liver was suggested by the finding of a correlation between the serum and the bile IgA antibody activity. IgG antibodies were only found in inflamed gall bladders. The bile was shown to have antibacterial activity against E. coli, i.e. an ability to inhibit the attachment to epithelial cells, but the inhibitory activity was not restricted to the immunoglobulin fraction of the bile.

Adhesiveness↗

PubMed1986

Bacterial adherence in urinary tract infections caused by Escherichia coli.

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Adhesiveness↗

PubMed1985

Non-antibody-containing fractions of breast milk inhibit epithelial attachment of Streptococcus pneumoniae and Haemophilus influenzae.

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Epithelium↗

PubMed1985

Defence of mucous membranes by antibodies, receptor analogues and non-specific host factors.

Most infections reach man via the mucosal membranes, and more than half of the lymphoid system is found in connection with mucosae. The major antibodies found on mucous membranes are secretory IgA, which function primarily by binding microorganisms and thereby preventing their contact with the host tissues. The optimal mode of immunization to obtain a secretory IgA response is not well defined. Repeated mucosal exposure with antigen may result in oral tolerance, with decreasing circulating antibodies but a remaining secretory IgA response. The secretory IgA response is usually short-lived and can be difficult to boost. IgM as well as IgG antibodies may add to host defence at the mucosal level, but when engaged, they usually induce inflammation in host tissues. Analogues to bacterial receptors on mucosal epithelium may be present in exocrine secretions such as human milk. During an attack on the host, it is possible that such receptor analogues may aid in the prevention of attachment of bacteria to mucous membranes used as an initial site. A number of non-specific host factors support mucosal defence. One of them is lactoferrin. Lactoferrin deficiency seems to result in recurrent bacterial infections, suggesting its importance in normal host defence.

Antibody Formation↗

PubMed1985

Genetic factors in host resistance to urinary tract infection.

In patients with recurrent pyelonephritis, the pathogenetic events proceed through intestinal colonization, spread to the urinary tract and persistence, seemingly uninterrupted by host defense mechanisms. The factors responsible for the deficient bacterial clearance from the kidneys of these patients, and the genetic control, have not been identified. The susceptibility to colonization has been linked to an increased receptivity for attaching bacteria of the uroepithelia, and to an overrepresentation of the P1 blood group phenotype. To evaluate the role of defects in host defense for the susceptibility to pyelonephritis, experimental UTI in mouse strains with known deficiencies was used. A highly significant increase in susceptibility was noted for C3H/HeJ compared to C3H/HeN mice. The bacterial recovery was inversely correlated to the mitogenic response to LPS. Back-cross analysis revealed a linkage of susceptibility to the Lpsd/Lpsd genotype. In contrast, T and B lymphocyte and complement (C5) defects had little effect on the clearance of Escherichia coli from the kidneys. It is concluded that the inflammatory mechanisms induced by LPS are essential for resistance to experimental pyelonephritis.

Animals↗

PubMed1985

Non-antibiotic prevention of urinary tract infection.

The identification of several glycoconjugates as receptors for attaching bacteria has resulted in optimism regarding the use of receptor analogues in preventing infection. The structure of receptor-active oligosaccharides and the patient groups which might benefit from such treatment are most thoroughly understood for urinary tract infections. Prevention of adhesion and delay or decrease of infection was achieved using oligosaccharides from the globoseries of glycolipids containing Gal alpha 1----4Gal. This minimal receptor structure as a free saccharide was, however, not sufficient. It was the intact P, P1 and pk determinants which showed optimal activity in vitro. In addition, protection against experimental UTI results from previous exposure to whole bacteria or isolated antigens. The mechanism(s) of protection and their relevance in clinical UTI remain to be defined.

Animals↗

PubMed1985

Urinary immunoglobulins in healthy individuals and children with acute pyelonephritis.

Urine samples obtained from children with acute pyelonephritis and from healthy children and adults were analysed with regard to the molecular form and specific antibody activity of urinary immunoglobulins. The urinary IgA and IgG levels were quantified in unconcentrated urine by radioimmunoassay. The children with urinary tract infection had significantly higher levels of IgG and IgA than age-matched controls but not higher than healthy adults. After tenfold concentration, the urine was fractionated on an Ultrogel AcA 22 column, and the IgA, secretory IgA, and IgG in the fractions were determined by radioimmunoassay. IgA in urine from healthy adults was predominantly represented by polymeric IgA linked to secretory component; small quantities of monomeric IgA were also present. IgG eluted in the position of the serum standard. Increased proportions of IgG and monomeric IgA were found in the infected patients. Specific antibody activity of the IgG and IgA classes to antigens of the infecting Escherichia coli strain was detected in whole and in fractionated urine from children with acute pyelonephritis. The specific antibody activity in healthy adults and children was low.

Acute Disease↗

PubMed1984

Virulence-associated traits in Escherichia coli causing first and recurrent episodes of urinary tract infection in children with or without vesicoureteral reflux.

Virulence-associated properties of 606 urinary isolates from 174 children with urinary tract infections were related to severity of infection and factors increasing host susceptibility, e.g., vesicoureteral reflux (grade II or higher) and P1 blood group phenotype. A high proportion of strains of Escherichia coli causing first or recurrent episodes of acute pyelonephritis in children without reflux expressed the previously noted high frequency of certain O antigens, resistance to serum killing, hemolysin production, and adhesive capacity. A significantly lower frequency of these traits and a higher frequency of non-E. coli were seen among isolates from children with pyelonephritis and reflux, cystitis, and asymptomatic bacteriuria. Reflux was thus found to be a determinant of the level of infection and of the bacterial properties required to produce pyelonephritis. Efforts aimed at preventing or treating urinary tract infection by interfering with "virulent" bacteria may be of less value in patients with recurrent pyelonephritis and reflux, who are most likely to develop renal scars.

Adhesiveness↗

PubMed1984

Influence of adhesins on the interaction of Escherichia coli with human phagocytes.

The fitness between bacterial adhesins and target cell receptors, determining bacterial adherence to epithelial cells in urinary tract infections, was shown to influence also the interaction with human polymorphonuclear leukocytes (PMNL). Two sets of homogenic strains, constructed to express either, both, or none of the globotetraosylceramide-sensitive (GS) adhesins specific for globoseries glycolipid receptors or the mannose-sensitive (MS) adhesins inhibited by alpha-methyl mannoside were compared regarding charge, hydrophobicity, and binding to PMNL. The mutants of a hydrophilic pyelonephritis strain required MS adhesins for binding to and activation of the PMNL. Removal of the MS adhesins from the mutant carrying both MS and GS adhesins abolished chemiluminescence and binding. A pronounced chemiluminescence reaction was induced by the hydrophobic strain without GS or MS adhesins . Transformants of this strain expressing the MS adhesin bound to and activated the PMNL. Poor binding and activation were found with mutants and transformants carrying only the GS adhesins . The improved reactivity after coating of the PMNL with the appropriate receptor glycolipid supported the previously reported absence of globoseries glycolipids in those cells as the reason for the refractoriness to bacteria with GS adhesins . The mechanism of binding, which improves epithelial cell adhesion, may prevent binding to PMNL, thus improving the survival of Escherichia coli in the kidney.

Adhesins, Escherichia coli↗