Role of inflammasome activation in the maturation of dendritic cells and in the development of adaptive imune response.

Author(s)

Thaís Boccia da Costa

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2014-08-07

Examining board members

Karina Ramalho Bortoluci; Renato Barboza; Alexandre de Castro Keller; Jean Pierre Schatzmann Peron; Alessandra Pontillo

• Advisor: Karina Ramalho Bortoluci

Abstract

TLR5 activates inflammatory genes through MyD88 pathway whereas NLRC4 and NAIP5 assemble multiprotein complexes called inflammasomes, leading to caspase-1 activation and secretion of proinflammatory cytokines IL-1 and IL-18. Cytosolic flagellin (FLA-BSDot) induced upregulation of costimulatory molecules independent on TLR5, NLRC4 and Caspase-1, but dependent on MyD88. In addition, FLA-BSDot-stimulated OVA-pulsed BMDCs induced proliferation and production of IFN by OT-II splenocytes, dependent on caspase-1 and MyD88. FLA-BSDot stimulation leads to the secretion of IL-1 and IL-1. Neutralization of IL-1 inhibited BMDCs maturation in response to FLA-BSDot and led to decreased IFN production by OT-II splenocytes. Searching for the effector mechanism by which IL-1 induces Th1 polarization in response to FLA-BSDot, we observed a significant reduction in IL-12 production when IL-1 was neutralized. Also, we could see that adaptive immune responses induced by flagellin in vivo was protective against S.typhimurium lethal challenge, showing again a role for caspase-1 and MyD88. From these data we can infer that caspase-1 and MyD88 are both involved in the adaptive response induced by flagelin both in vitro and in vivo. (AU)

• FAPESP's process: 11/12639-0 - Role of inflammasomes in dendritic cell maturation and induction of adaptive responses.
• Grantee: Thaís Boccia da Costa
• Support Opportunities: Scholarships in Brazil - Doctorate