Mucosal IFN-¿ production and potential role in protection in Escherichia coli O157:H7 vaccinated and challenged cattle

Authors: SCHAUT, ROBERT - Orise Fellow; Palmer, Mitchell; Boggiatto, Paola; Kudva, Indira; Loving, Crystal; Sharma, Vijay

Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/14/2021
Publication Date: 5/7/2021
Citation: Schaut, R.G., Palmer, M.V., Boggiatto, P.M., Kudva, I.T., Loving, C.L., Sharma, V.K. 2021. Mucosal IFN-¿ production and potential role in protection in Escherichia coli O157:H7 vaccinated and challenged cattle. Infection and Immunity. 11. Article 9769. https://doi.org/10.1038/s41598-021-89113-7.
DOI: https://doi.org/10.1038/s41598-021-89113-7

Interpretive Summary: Escherichia coli O157:H7 (O157) bacterial infections in humans can result in mild diarrheal illness to an illness accompanied with bloody diarrhea. Cattle are considered the major reservoir for O157 bacteria and majority of human O157 infections result from the consumption of meats, vegetables or water that come in contact with cattle feces/manure. Thus, reducing fecal shedding of O157 in cattle is an important intervention for reducing transmission of O157 to humans. We previously showed that vaccinating cattle with a modified and killed O157 bacteria combined with an appropriate immune system stimulating agent (adjuvant) can reduce fecal shedding of O157 by about 50 percent. Therefore, to achieve reductions higher than 50 percent in O157 fecal shedding, it is important to understand how these vaccines work in terms of immune system activation in cattle. In this current study, we found that cattle vaccinated with modified O157 bacteria mixed with a specific adjuvant capable of reducing fecal shedding of O157 enhanced the levels of specific immune cells and specific immune proteins produced by these cells. We further showed that treatment of bovine epithelial cell lines with one of these immune proteins reduced the ability of O157 to attach to these epithelial cells. This is a very important result as this would facilitate testing of additional vaccines and adjuvants to determine if the levels of these particular immune cells and/or immune proteins can be enhanced to achieve greater reductions in colonization and fecal shedding of O157 in cattle.

Technical Abstract: Parenterally-delivered, adjuvanted bacterin-based vaccines can significantly limit shedding of Shiga-toxin producing Escherichia coli O157:H7 (O157) in cattle feces, providing a potential intervention strategy to limit foodborne transmission of O157 to humans. While the peripheral antibody response to O157 following bacterin vaccinated has been characterized, O157-specific cellular immunity at the rectoanal junction (RAJ), a preferred site for O157 colonization, remains poorly described. While vaccine induced mucosal O157-specific antibodies likely provide some protection, cellular immune responses may also contribute to limiting O157 colonization at the RAJ. Distinct lymphoid follicles were increased in the RAJ of vaccinated/challenged animals. In addition, increased numbers of interferon (IFN)-gamma-producing cells and a subset of gamma delta plus T cells were detected in the follicular region of the RAJ of vaccinated/challenged animals. The inclusion of adjuvant in the bacterin significantly impacted the number of IFN-gamma producing cells in the RAJ, indicating vaccine formulation is critical in immunogenicity of the O157 parenteral vaccine. Local T cell produced IFN-gamma may impact epithelial cells, subsequently limiting O157 adherence, which was demonstrated using in vitro attachment assays with bovine epithelial cells. Thus, distinct immune changes induced at the mucosa of vaccinated and challenged animals provides insight in to mechanisms associated with limiting O157 fecal shedding. Enhancing mucosal immunity may be critical in the further development of efficacious vaccines for controlling O157 in ruminants and thus limiting O157 transmission to humans.