| dc.description.abstract | Shiga producing E. coli (STEC) O157 is a zoonotic pathogen. In humans STEC O157 causes
bloody diarrhoea and potentially fatal renal failure. Cattle are the major reservoir, where
bacteria are limited to the intestinal tract and do not cause clinical signs of disease. Previous
studies indicate that shiga toxins produced by STEC O157, suppress STEC-specific cellular
immune responses in vivo.
This study aimed to initially examine the humoral immune response in cattle following
natural challenge and the effects of a toxoid vaccination on this humoral STEC specific-immune
response. We determined a statistically significant suppression in Tir specific IgA in
STEC O157 positive cattle compared to O157 negative cattle but not in super shedding
cattle. Following toxoid vaccination we determined a significant increase in flagellin specific
IgG1 antibody levels in toxoid vaccinated animals despite lower numbers of positive faecal
samples compared to placebo vaccinated controls. These results suggest that shiga toxins
produced by STEC O157 are actively suppressing the STEC specific immune response in
natural colonisation. To clarify this suppression further calves were orally challenged with
STEC O157 (either a PT21/28 Stx2c+, PT32 Stx2c+ or PT21/28 Stx2a+Stx2c+ strain) and
their STEC specific immune responses monitored. STEC specific systemic antibody
responses were variable and weak in some cases. STEC specific local antibody responses
were only significantly increased following challenge with the PT21/28 Stx2a+Stx2c+
challenge. Transcripts for genes associated with immune responses, and in particular B cell
activation, at the terminal rectum were analysed by reverse transcriptase quantitative PCR.
Suppression of IL2RA transcripts was observed in calves challenged with PT21/28
Stx2a+Stx2c+ compared to control calves but not with the other two STEC O157 strains
tested.
This study also aimed to determine the effects of cattle colonisation with STEC O157 on the
immune response to a non-bacterial T-cell dependent antigen, ovalbumin (OVA). Cattle
were orally challenged with either a PT21/28 Stx2c+, PT32 Stx2c+ or PT21/28
Stx2a+Stx2c+ strain or unchallenged. Calves were subcutaneously immunised with OVA
five days post challenge, on two separate occasions with a two week interval. Lymphocytes
from lymph nodes local to the immunisation site demonstrated significantly increased OVA-specific
proliferation and OVA-specific activation of CD4+ and CD8+ cells in calves that
were challenged with the PT21/28 Stx2c+ strain (but not with the other two challenge
strains), compared to unchallenged controls. These results indicate that colonisation with
STEC O157 can alter local adaptive immune responses to non-bacterial antigens in a strain
dependent manner, unexpectedly enhancing the immune response rather than suppressing it.
Circulating T cell responses were unaffected.
In conclusion this study provides some further evidence of adaption of the host immune
response by STEC O157, which is strain dependent, and variable. It seems unlikely from the
data in this study that STEC O157 colonisation is having a major impact on the responses of
cattle to other vaccines or infections in the field. | en |
