CONICET | Buscador de Institutos y Recursos Humanos

Introduction: During the acute stage ofgastrointestinal infection, the interaction between local antigen-presentingcells and STEC strains leads to the activation of mucosal CD4+ T lymphocyteswith the consecutive release of pro-inflammatory cytokines that contributes toan effective immune response but also to a possibly deleterious inflammation. Theaim was to assess the involvement of dendritic cells (DCs) in the local immuneresponse as well as the cytokine profile induced in a mouse model of HUS byintragastrically administered STEC strains. Methods: We evaluated DC subsets (CD11b+, CD8α+, CD11b-/CD8α-) by flow cytometry, and in vitro proliferation and cytokineproduction (IL10, IL17, IL6, IL4) by lymphocytes from mesenteric lymph nodes(MLN) by MTT assay and ELISA respectively, at 10 h after infection. Tounderstand the role of Stx in the local immune activation, we administered the isogenicStx-negative strain (ΔStx) in a group of mice. Data were compared by ANOVAfollowed by comparison between treatments by SNK test, p < 0.05.Results and Discussion: We observed a significantlyincreased percentage of CD11b+ DCs in MLN from STEC- and ΔStx-inoculatedanimals compared to control (PBS-inoculated) [mean %±SEM,n]: Ctrol=26.11±3.03,3; ΔStx=38.70±2.54, 5; STEC=38.96±2.86, 5. Simultaneously, there was asignificant increased number of pre-activated lymphocytes as well as increasedlevels of IL10, IL17 and IL6 in both bacterial-inoculated mice when stimulatedwith CD3/CD28 in vitro. Proliferation[mean OD570±SEM,n]: Ctrol=0.28±0.04, 6;ΔStx=0.53±0.02, 7; STEC=0.48±0.04, 14. IL17 [mean pg/ml ±SEM,n]: Ctrol=22.2±6.2,9; ΔStx=203.0±62.8, 7; STEC=127.6±50.3, 10. On the other hand, IL4 wassignificantly increased only in ΔStx-inoculated animals: Ctrol=158±24, 10;ΔStx=295±37, 7; STEC=143±25, 14. Although both bacterial strains induced asimilar local immune activation and cytokine profile, ΔStx strain determinedhigher levels in cytokine release.Implications: Stx production could limit localinflammation and this would benefit STEC persistence in host intestine, thusfavoring HUS outcome.

enviar mensaje