Mouse fibroblasts guide IL-23 induction by Porphyromonas gingivalis-stimulated Dendritic Cells in gingipain-dependent manner
Ana C. Morandini: 0000-0003-4749-571X
EUROPERIO 7 - 7th Conference of the European Federation of Periodontology
European Federation of Periodontology
June 6-9, 2012
Date of Presentation
Aim: In a previous study, we reported that bradykinin release in BALB/c subgingival tissues exposed to P.gingivalis induces IL17-producing and INF-γ producing T cells in gingipain-dependent manner (Monteiro et al., J.Immunol. , 2009). Here, we sought to determine whether (i) bone marrow derived DCs exposed to P.gingivalis (W83) versus gingipain-deficient mutants (KRAB) differentially produce IL-23, i.e., a key Th17-polaring cytokines (ii) gingival fibroblasts (GF) may modulate the response profile of immature DCs (IL-23 and CCR7) in gingipain-dependent manner.
Material and Methods: Mouse BMDCs were co-cultured with mouse GFs and stimulated with P. gingivalis LPS (0.1 ug/mL), P. gingivalis (strain W83) or a triple gingipain knockout P. gingivalis (KRAB) for 24 h. Subsequently, the supernatants were collected and IL-23 levels were quantified by ELISA whereas CCR7 expression by CD11c+ DCs was determined by FACS.
Results: Our results indicate that bacteria-exposed GF/DCs led to a prounced enhancement of IL-23 responses by the CD11c+ DCs partner, as compared to (i) cultures containing only DCs (ii) GF/DC co-cultures exposed to the KRAB mutant. Furthermore, CCR7 expression, likewise dependent on gingipain, was upregulated independently of co-culturing with GF.
Conclusion: Our results suggest that GFs condition the functional responses of immature DCs, shifting P.gingivalis-evoked maturation responses towards the IL-23 innate pathway. Ongoing studies should determine the role of GF versus DCs on the gingipain/bradykinin B2 receptor pathway leading to Th17 polarization in BALB/c mice infected by P.gingivalis.
Ramos-Junior, E. S.,
Morandini, A. C.,
Mouse fibroblasts guide IL-23 induction by Porphyromonas gingivalis-stimulated Dendritic Cells in gingipain-dependent manner.
Paper presented at EUROPERIO 7 - 7th Conference of the European Federation of Periodontology in Vienna, Austria.