Adenylate cyclase toxin (CyaA) is a key virulence factor of the whooping cough agent Bordetella pertussis. The toxin targets CD11b-expressing phagocytes and delivers into their cytosol an adenylyl cyclase (AC) enzyme that subverts cellular signaling by increasing cAMP levels. In the present study, we analyzed the modulatory effects of CyaA on adhesive, migratory and antigen presenting properties of Toll-like receptor (TLR)-activated murine and human dendritic cells (DCs). cAMP signaling of CyaA enhanced TLR-induced dissolution of cell adhesive contacts and migration of DCs towards the lymph node-homing chemokines CCL19 and CCL21 in vitro. Moreover, we examined in detail the capacity of toxin-treated DCs to induce CD4(+) and CD8(+) T cell responses. Exposure to CyaA decreased the capacity of LPS-stimulated DCs to present soluble protein antigen to CD4+ T cells independently of modulation of co-stimulatory molecules and cytokine production, and enhanced their capacity to promote CD4(+)CD25(+)Foxp3(+) T regulatory cells in vitro. In addition, CyaA decreased the capacity of LPS-stimulated DCs to induce CD8(+) T cell proliferation and limited the induction of IFN-γ producing CD8(+) T cells while enhancing IL-10 and IL-17-production. These results indicate that through activation of cAMP signaling, the CyaA may be mobilizing DCs impaired in T cell stimulatory capacity and arrival of such DCs into draining lymph nodes may than contribute to delay and subversion of host immune responses during B. pertussis infection.
- MeSH
- adenylátcyklasový toxin farmakologie MeSH
- aktivace lymfocytů účinky léků MeSH
- Bordetella pertussis chemie MeSH
- buněčná adheze účinky léků MeSH
- buněčná smrt účinky léků MeSH
- CD antigeny metabolismus MeSH
- CD8-pozitivní T-lymfocyty cytologie účinky léků imunologie MeSH
- dendritické buňky cytologie účinky léků imunologie MeSH
- lidé MeSH
- myši inbrední C57BL MeSH
- pohyb buněk účinky léků MeSH
- proliferace buněk účinky léků MeSH
- regulační T-lymfocyty účinky léků MeSH
- rozpustnost MeSH
- toll-like receptory metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
