The major objective of this investigation is to determine the role of the host's inflammatory response in the pathogenesis of an enteric disease. The cellular mechanisms underlying the causes of intestinal diseases are not fully delineated. Although, it appears that the host's own immune system may mediate significant portion of the tissue injury. This project will focus on the host's inflammatory and T cell mediated responses and the involvement of this responsiveness in the development of an inflammatory colitis in mice. Lipopolysaccharide-responsive C3H/HeOuJ and LPS-hyporesponsive C3H/HeJ mice will be infected with a mucosal pathogen, Serpulina (Treponema) hyodysenteriae. The histopathological changes in the tissues will be examined by routine histological stains and by examining the tissue for the changes in the ratio of helper (CD4+) and suppressor (CD8+) T cells. In addition, spectral changes in the level or type of cytokines secreted in relation to the infection and LPSresponsiveness of the mice will be examined. Isolated T cells from control and infected mice will be analysed for the production of gamma interferon (IFN-g) or interleukin 5 (IL 5). These profiles will allow us to determine whether or not there are any differences between the two mouse strains in their T cell responses and whether this difference correlates with resistance to disease. It is anticipated that inflammatory cytokines will be involved in the pathogenesis; and, therefore, the increased production of IL 1, tumor necrosis factor (TNF), and IFN-g will be observed following infection with S. hyodysenteriae. This will be measured by extracting total RNA from cells of the lamina propria These RNA preparations will be examined for increases in cytokine specific mRNA by Northern blot analysis. Serpulina hyodysenteriae was chosen as the disease model because it induces a chronic mucohemorrhagic diarrheal disease. In addition, the organism does not invade beyond the lamina propria which will reduce the contributory effects of systemic responses which would be induced by a more invasive organism (i.e., Salmonella typhimurium). It is hoped that the proposed studies will increase the understanding of the mechanisms involved in the induction of inflammatory diseases and provide some insight into the role of immune cells play in the induction, of, resolution of or protection from intestinal lesion development.
| Sacco, R E; Nibbelink, S K; Baarsch, M J et al. (1996) Induction of interleukin (IL)-1beta and IL-8 mRNA expression in porcine macrophages by lipopolysaccharide from Serpulina hyodysenteriae. Infect Immun 64:4369-72 |
