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Targeting of F4 fimbriae to Fc receptors enhances the maturation of porcine monocytic-derived dendritic cells

Bert Devriendt (UGent) , Frank Verdonck, Bruno Goddeeris (UGent) and Eric Cox (UGent)
Author
Organization
Abstract
F4+ enterotoxigenic E. coli (ETEC) adhere with their F4 fimbriae to an F4-specific receptor, colonise the small intestine and cause diarrhoea in recently weaned piglets. Our group has demonstrated that oral immunisation of piglets with purified F4 fimbriae induces an F4-specific immune response, which protects these piglets against an F4+ ETEC infection. However, to protect against postweaning diarrhoea, immunisation should already occur during the suckling period. At this age, oral immunisation could be complicated due to the immature status of the immune system. Furthermore, F4 fimbriae only partially mature intestinal dendritic cells. A possible solution could be targeting the antigen to Fc receptors (FcR) present on antigen presenting cells, as this can enhance the cellular and humoral immune response. Therefore, we determined the effects of F4-IgG immune complexes (IC) on maturation of porcine monocytic-derived dendritic cells (MoDC). As expected, IC induced a higher upregulation of the costimulatory molecules CD80/86 and CD40 and of the antigen presenting molecule MHCII as compared to F4 and IgG treated cells. Moreover, IC stimulation downregulated both the phagocytic (OVA-dQ) and endocytic capacity (FITC-dextran), whereas F4 and IgG stimulation only resulted in a moderate reduction. To further investigate whether the mature phenotype of the MoDC after IC treatment correlate with their capacity to stimulate T cells, MoDC were cocultured with allogeneic T lymphocytes. Thus, IC matured MoDC were more effective at activating allogeneic T cells in comparison to F4 and IgG treated cells. Together, these results show that IC enhance the maturation of porcine MoDC. Mature MoDC secrete a wide range of cytokines, determining the outcome of adaptive immune responses. IC matured MoDC secreted higher levels of IL-1β, IL-6, IL-8, IL-12p40 and TNFα cytokines as compared to F4 and IgG treated MoDC. These findings clearly indicate that antigen targeting to FcR enhances the maturation of porcine MoDC and that this maturation involves a heightened secretion of several inflammatory cytokines.

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MLA
Devriendt, Bert, et al. “Targeting of F4 Fimbriae to Fc Receptors Enhances the Maturation of Porcine Monocytic-Derived Dendritic Cells.” International Symposium on Dendritic Cells, 10th, Abstracts, 2008.
APA
Devriendt, B., Verdonck, F., Goddeeris, B., & Cox, E. (2008). Targeting of F4 fimbriae to Fc receptors enhances the maturation of porcine monocytic-derived dendritic cells. International Symposium on Dendritic Cells, 10th, Abstracts. Presented at the 10th International symposium on Dendritic Cells (DC2008), Kobe, Japan.
Chicago author-date
Devriendt, Bert, Frank Verdonck, Bruno Goddeeris, and Eric Cox. 2008. “Targeting of F4 Fimbriae to Fc Receptors Enhances the Maturation of Porcine Monocytic-Derived Dendritic Cells.” In International Symposium on Dendritic Cells, 10th, Abstracts.
Chicago author-date (all authors)
Devriendt, Bert, Frank Verdonck, Bruno Goddeeris, and Eric Cox. 2008. “Targeting of F4 Fimbriae to Fc Receptors Enhances the Maturation of Porcine Monocytic-Derived Dendritic Cells.” In International Symposium on Dendritic Cells, 10th, Abstracts.
Vancouver
1.
Devriendt B, Verdonck F, Goddeeris B, Cox E. Targeting of F4 fimbriae to Fc receptors enhances the maturation of porcine monocytic-derived dendritic cells. In: International symposium on Dendritic Cells, 10th, Abstracts. 2008.
IEEE
[1]
B. Devriendt, F. Verdonck, B. Goddeeris, and E. Cox, “Targeting of F4 fimbriae to Fc receptors enhances the maturation of porcine monocytic-derived dendritic cells,” in International symposium on Dendritic Cells, 10th, Abstracts, Kobe, Japan, 2008.
@inproceedings{783091,
  abstract     = {{F4+ enterotoxigenic E. coli (ETEC) adhere with their F4 fimbriae to an F4-specific receptor, colonise the small intestine and cause diarrhoea in recently weaned piglets. Our group has demonstrated that oral immunisation of piglets with purified F4 fimbriae induces an F4-specific immune response, which protects these piglets against an F4+ ETEC infection. However, to protect against postweaning diarrhoea, immunisation should already occur during the suckling period. At this age, oral immunisation could be complicated due to the immature status of the immune system. Furthermore, F4 fimbriae only partially mature intestinal dendritic cells. A possible solution could be targeting the antigen to Fc receptors (FcR) present on antigen presenting cells, as this can enhance the cellular and humoral immune response. 
Therefore, we determined the effects of F4-IgG immune complexes (IC) on maturation of porcine monocytic-derived dendritic cells (MoDC). As expected, IC induced a higher upregulation of the costimulatory molecules CD80/86 and CD40 and of the antigen presenting molecule MHCII as compared to F4 and IgG treated cells. Moreover, IC stimulation downregulated both the phagocytic (OVA-dQ) and endocytic capacity (FITC-dextran), whereas F4 and IgG stimulation only resulted in a moderate reduction. To further investigate whether the mature phenotype of the MoDC after IC treatment correlate with their capacity to stimulate T cells, MoDC were cocultured with allogeneic T lymphocytes. Thus, IC matured MoDC were more effective at activating allogeneic T cells in comparison to F4 and IgG treated cells. Together, these results show that IC enhance the maturation of porcine MoDC. Mature MoDC secrete a wide range of cytokines, determining the outcome of adaptive immune responses. IC matured MoDC secreted higher levels of IL-1β, IL-6, IL-8, IL-12p40 and TNFα cytokines as compared to F4 and IgG treated MoDC. These findings clearly indicate that antigen targeting to FcR enhances the maturation of porcine MoDC and that this maturation involves a heightened secretion of several inflammatory cytokines.}},
  author       = {{Devriendt, Bert and Verdonck, Frank and Goddeeris, Bruno and Cox, Eric}},
  booktitle    = {{International symposium on Dendritic Cells, 10th, Abstracts}},
  language     = {{eng}},
  location     = {{Kobe, Japan}},
  title        = {{Targeting of F4 fimbriae to Fc receptors enhances the maturation of porcine monocytic-derived dendritic cells}},
  year         = {{2008}},
}