Forschungs- & Entwicklungsinformationsdienst der Gemeinschaft - CORDIS

Inflammatory and immune response during AEEC infection in rabbits

The objectives of this work package were to understand the physiopathology of AEEC infections using rabbit, a relevant animal host highly susceptible to EPEC. We aimed at defining the importance of the strong inflammatory response in the development of the disease and at characterising bacterial effectors responsible for this inflammation.

Major finding during the project:
Rabbit EPEC infection induced dramatic villus atrophy in the distal ileum combined with a hypertrophy of the glandular region. Epithelial cells were irregular and dysplastic and strong exfoliation occurred. The brush border was not visible. Similar lesions were observed in the proximal colon. In contrast, 5 days after inoculation of a Tir/EspB mutant, there were no architectural intestinal modifications in the ileum or the colon. Villi were preserved and no inflammation was detectable. Epithelial cells were regular and the brush border was visible and comparable to that of the ileum of control rabbits. A new collaboration with a Mexican team allowed us to analyse the expression of proinflammatory cytokines from enterocytes and lymphocytes by EPEC-Infected rabbits and to study the role of EspA and intimin.

Orally inoculated rabbits suffered from weight loss, mucosa inflammation, developed watery diarrhea, and died (day 7). At day 6 postinoculation, animals were analyzed for induction of proinflammatory cytokines in enterocytes. The role of lymphocyte-dependent immunity was determined through expression of proinflammatory cytokines by lymphocytes from Peyer's patches and spleen. EspA and intimin mutants were used to explore the role of the A/E lesion on the expression of these cytokines. Infected rabbit enterocytes increased IL-1b, IL-6, IL-8 and TNF-a mRNAs expression (by RT-PCR) but only slightly the anti-inflammatory IL-10. In contrast, intimin mutant-infected rabbits were unable to induce this proinflammatory cytokine profile but did induce a remarkable increase of IL-10.

Whereas, EspA mutant increased the expression of IL-8 and TNF-a but only slightly IL-10. Peyer's patches lymphocytes (PP) also produced proinflammatory cytokines, which were dependent on EspA (except TNF-a) and intimin, while IL-10 was induced by EspA and intimin mutants. In contrast, spleen lymphocytes (systemic compartment) were unable to induce IL-1b and TNF-a. These data show the importance of the proinflammatory cytokines secreted by enterocytes and those expressed locally by PP lymphocytes, which can activate effector mechanisms at the epithelium. Furthermore, this cytokine profile depends on intimin, including IL-6 and IL-1b, which may be involved in the diarrhoea produced by EPEC.

Reported by

INRA-ENVT Microbiologie
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