| First Author | Cross A | Year | 1995 |
| Journal | J Clin Invest | Volume | 96 |
| Issue | 2 | Pages | 676-86 |
| PubMed ID | 7635960 | Mgi Jnum | J:27736 |
| Mgi Id | MGI:75221 | Doi | 10.1172/JCI118110 |
| Citation | Cross A, et al. (1995) The importance of a lipopolysaccharide-initiated, cytokine-mediated host defense mechanism in mice against extraintestinally invasive Escherichia coli. J Clin Invest 96(2):676-86 |
| abstractText | Extraintestinally invasive Escherichia coli (EC) that possess both a complete LPS and K1 capsule evade both complement-mediated bacteriolysis and neutrophil-mediated killing. Since C3H/HeJ mice that are hyporesponsive to LPS were uniquely susceptible to lethal infection with EC of this phenotype, we speculated there was an LPS-initiated host defense mechanism against this pathogenic phenotype. The LPS-normoresponsive C3H/HeN as well as the C3H/HeJ mice cleared these EC from the circulation within 4 h of intravenous administration. Whereas electron micrographs of the liver demonstrated these EC undergoing degeneration within the phagolysosomes of of both macrophages and Kupffer cells of C3H/HeN mice, these EC replicated within these cells of the C3H/HeJ mice. Restoration of anti-EC activity of C3H/HeJ mice occurred with activation of Kupffer cells and peritoneal macrophages in vivo with BCG and in vitro with IFN-gamma, but not with LPS. Pretreatment of C3H/HeJ mice with a combination of recombinant murine IL-1 and TNF-alpha also restored the killing of K1(+)-EC but did not enhance the killing of a K1(-)-EC mutant. These data are consistent with the hypothesis that (a) there is no intrinsic inability of C3H/HeJ phagocytes to kill EC, but (b) an LPS-initiated, cytokine-mediated host defense mechanism is required for such killing. These studies emphasize the importance of bacterial surface characteristics in the interaction with specific host defenses. |
