CD4⁺ T‐cell responses and distribution at the colonic mucosa during Brachyspira hyodysenteriae‐induced colitis in pigs

Abstract

Summary The spirochaete Brachyspira hyodysenteriae causes swine dysentery, a severe colitis characterized by mucosal enlargement as a result of crypt elongation and epithelial necrosis. Most efforts to understand the pathogenesis of this disease have focused on the aetiological agent and its virulence factors. However, the host immune response has been considered an important factor in disease development. Previous research has shown that B. hyodysenteriae induces systemic CD4+ and γδ T‐cell responses after intramuscular immunization. Here, we have evaluated changes in the CD4+ and γδ T‐cell composition and distribution the different compartments of the colonic mucosa of pigs challenged with B. hyodysenteriae. We report that, in infected pigs, γδ T cells were significantly depleted from the epithelial layer, although their numbers were maintained in the lamina propria. In addition, CD4+ T cells aggregated in clusters located in the lamina propria and submucosa. Ex vivo analyses of CD4+ T‐cell responses to B. hyodysenteriae antigens correlated with the changes in the mucosal CD4+ T‐cell distribution observed in infected pigs; CD4+ T cells recovered from peripheral blood and colonic lymph nodes of infected pigs proliferated to B. hyodysenteriae antigens, whereas no differences were found in the γδ T‐cell responses between challenged and control groups. In addition, colonic lymph node CD4+ T cells had a predominant memory/activated phenotype. These results indicate that infection with B. hyodysenteriae induces a mucosal CD4+ T‐cell response and points to CD4+ T cells being important contributors to the immunopathogenesis of swine dysentery.

Diverse Intestinal Bacteria Contain Putative Zwitterionic Capsular Polysaccharides with Anti-inflammatory Properties

“…Consistent with this notion, infection with putative ZPS-producer B. hyodysenteriae , which induces a severe colitis in pigs known as swine dysentery, induces a mucosal CD4 + T-cell response. This suggests that the induction of both pro-inflammatory and regulatory responses are important in the pathogenesis of this species (Hontecillas et al 2005). …”

An Activated Immune and Inflammatory Response Targets the Pancreas of Newborn Pigs with Cystic Fibrosis

“…The role of γδ T cells in the pig immune system is poorly understood. γδ T cells can downregulate inflammatory responses [36,37] and constitute a first line of defense at mucosal surfaces, representing a link between innate and adaptive immunity [38,39]. It is possible that γδ T cells are activated in CF pig pancreas as a reaction to the inflammatory response and provide crosstalk between the innate and adaptive immune systems.…”

Nutritional protective mechanisms against gut inflammation

“…We have also developed a bacterial-induced model of colitis in pigs, in which pigs are challenged with two doses of 10 10 colony forming units of Brachyspira hyodysenteriae given in two consecutive days to study the anti-inflammatory effects of CLA. This model results in dysentery, a severe mucohemorrhagic diarrheal disease and colitis characterized by mucosal enlargement as a result of crypt elongation and epithelial necrosis [32,33]. We have used the Gn pig model of human rotavirus infection to characterize the dose effects of probiotic Lactobacillus rhamnosus GG and L. acidophilus NCFM strains on APC, natural and induced Treg cell, IFN-γ-producing T cell, and B cell responses in the intestinal and systemic lymphoid tissues [34].…”