Nonlethal adherence to human neutrophils mediated by Dr antigen-specific adhesins of Escherichia coli

Abstract

Escherichia coli strains express a variety of adhesins, including members of the Dr adhesin family such as the Dr hemagglutinin, AFAI, and AFAIII. Certain E. coli adhesins (e.g., type 1 and S fimbriae) are known to mediate adherence to human polymorphonuclear leukocytes (PMNs). The receptor on erythrocytes for Dr family adhesins, decay accelerating factor, is also present on PMNs. To determine whether Dr family adhesins mediate adherence to PMNs and to characterize the specificity and consequences of such adherence, we studied agglutination of PMNs and adherence to PMNs by recombinant E. coli strains expressing various mannose-resistant or mannose-sensitive adhesins, in the presence or absence of inhibitors of adherence. Dr family adhesins, like type 1 fimbriae, mediated concentration-dependent adherence to PMNs. Adherence to PMNs was mannose sensitive for type 1 fimbriae but mannose resistant for Dr family adhesins. Chloramphenicol inhibited PMN adherence for the Dr hemagglutinin with the same potency as that with which it inhibited hemagglutination, but it was inactive against PMN adherence and hemagglutination mediated by other members of the Dr adhesin family. In contrast to PMN adherence mediated by type 1 fimbriae, adherence mediated by the Dr hemagglutinin did not lead to significantly increased bacterial killing. These data suggest that Dr family adhesins mediate a novel pattern of adherence to PMNs, probably by recognizing decay accelerating factor, with minimal consequent bacterial killing.

Pathogenesis of Afa/Dr Diffusely AdheringEscherichia coli

“…Importantly, in a Drpositive strain, the induction of PMNL cell death is independent of recognition of DAF, CEACAM1, and CEA. An increased rate of apoptosis was linked to the agglutination process developed by Dr adhesin, a phenomenon also observed by Johnson et al (211). Moreover, PMNLs that had transmigrated showed increased phagocytic activity towards E. coli (191).…”

“…Concomitantly with internalization, other cellular events contribute to the recurrence of infection by Afa/Dr DAEC. For example, Dr adhesin mediates the adherence of Afa/Dr DAEC to polymorphonuclear leukocyte (PMNLs), resulting in minimal bacterial killing (211). Moreover, the Afa/Dr DAEC strain C1845 induces F-actin-dependent long, thin membrane processes that extend from the cell surface (85).…”

“…(III) A MAPK-dependent signaling mechanism (circle 5) leads to the production of the proinflammatory cytokine IL-8, which triggers the transepithelial migration of PMNLs (circle 6) (39). Afa/Dr DAEC bacteria interact with PMNLs (circle 7) (57,211). In turn, PMNL transmigration promotes the production of proinflammatory cytokines TNF-␣ and IL-1␤ (circle 8) (40).…”

Pathogenesis of Human Diffusely Adhering Escherichia coli Expressing Afa/Dr Adhesins (Afa/Dr DAEC): Current Insights and Future Challenges

“…Adherence to hDAF expressed at the membrane of freshly isolated PMNLs mediated by Dr adhesin did not lead to a significant increase of bacterial killing, indicating that the Afa/Dr DAEC could overcome the microbicidal activity of PMNLs (472). In contrast with the fact that PMNLs that have transmigrated display greater phagocytic activity against E. coli (473), PMNLs that have not transmigrated or transmigrated across T84 cell monolayers after Afa/Dr DAEC infection display low phagocytic activity, suggesting that Afa/Dr DAEC can block this activity (453).…”

“…Interaction of the wild-type Afa/Dr DAEC C1845 and IH11128 strains or recombinant Dr adhesin-positive E. coli with freshly isolated human PMNLs results in an increased rate of cell apoptosis evidenced by morphological nuclear changes, DNA fragmentation, cleavage of pro-caspase 3 and stimulation of the caspase activity, and up-expression of annexin V (453,472). Since this phenomenon is not blocked by anti-hDAF and -hCEA antibodies, it seems to be linked to a leukocyte agglutination process rather than to the recognition of these signaling receptors.…”