Submitted to: Clinical and Vaccine Immunology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 10/5/2006
Publication Date: 12/20/2006
Citation: Hoffman, M.A., Menge, C., Casey, T., Laegreid, W.W., Bosworth, B.T., Nystrom, E.A. 2006. Bovine immune response to Shiga-toxigenic Escherichia coli O157:H7. Clinical and Vaccine Immunology. 13(12):1322-1327. Interpretive Summary: Escherichia coli O157:H7 and other enterohemorrhagic E. coli (EHEC) are foodborne pathogens that cause severe diarrhea and sometimes kidney failure and death in humans. Cattle are a major animal source of the human pathogen Escherichia coli O157:H7. Reduction of the levels of O157:H7 in the cattle population would have a positive impact on the frequency of human exposure to this pathogen. The objectives of this study were to monitor over time the development of specific immune responses in calves experimentally inoculated with either Stx-producing (Stx+) or Stx-negative (Stx-) strains of E. coli O157:H7, and to determine if immune responses affect the level and duration of fecal shedding of E. coli O157:H7 in experimentally inoculated animals. Three groups of calves (5 calves/group) were inoculated with different E. coli strains, twice in a 3-week interval. Group I received a wild-type Stx2+ E. coli O157:H7 strain (Stx2+O157); Group II, an O157:H7 isolate that does not produce Shiga toxin (Stx-O157); and Group III, a non-pathogenic E. coli (control). All three groups were challenged with Stx2+O157 after three additional weeks. Fecal shedding of Stx2+O157 was significantly higher than Stx-O157 or control. We found that an immune response to E. coli O157:H7 did not reduce fecal shedding of this pathogen in the early phase after experimental inoculation, and that Stx2 had an immunosuppressive effect in experimentally inoculated calves. This evidence that infections with Stx+ E. coli O157:H7 prevent the onset of specific cellular immune responses in cattle must be addressed in designing vaccines against E. coli O157:H7 infections in cattle.
Technical Abstract: Although cattle develop humoral immune responses to shiga-toxigenic E. coli (STEC) O157:H7, infections often result in long-term shedding of these human pathogenic bacteria. The objective of this study was to examine the effect of Stx in vivo on humoral and cellular immune responses to E. coli O157:H7. Three groups of calves were inoculated intra-rumenally, twice in a three-week interval, with different strains of E. coli: a Stx2-producing E. coli O157:H7 strain (Stx2+O157), a Shiga toxin-negative E. coli O157:H7 strain (Stx-O157), or a non-pathogenic E. coli (control). Three weeks after the second inoculation, all calves were challenged with Stx2+O157. Fecal shedding of Stx2+O157 was significantly higher than that of Stx-O157 control. Following the final challenge, fecal shedding of Stx2+O157 was similar in all three groups. Both groups inoculated with an O157 strain developed antibodies to O157 LPS. Calves initially inoculated with Stx-O157, but not those inoculated with Stx2+O157, developed a lymphoproliferative response to heat-killed Stx2+O157. These results provide evidence that infections with STEC can suppress the development of specific cellular immune responses in cattle, a finding that will need to be addressed in designing vaccines against E. coli O157:H7 infections in cattle.